Microbial biosynthesis of quantum dots: regulation and application

Abstract

Quantum dots (QDs) are nanoscale semiconductor materials that have found wide applications in fields such as biosensing and solar cells. Conventionally, QDs are synthesized chemically, but biosynthetic methods using microorganisms have been developed as an alternative strategy. Microbially biosynthesized QDs possess better biocompatibility than chemically synthesized QDs due to the proteins and peptides attached to their surfaces. In this review, we outline the recent advances in the biosynthesis of QDs using microorganisms including bacteria, fungi, and viruses. We also discuss the current understanding of the regulation of the biosynthetic process by extracellular and intracellular factors. Additionally, we highlight the potential of QD–microbe biohybrids self-assembled in the process of QD biosynthesis.

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1. Introduction

A decrease in the sizes of nanomaterials contributes to unique physical properties, such as large specific surface areas, changes in surface charge, and quantum size effects.^1–6 The quantum size effect and quantum dots (QDs) were first reported in the late 1970s.⁷ QDs are nanoscale semiconductor materials that are usually composed of IV, II–VI, IV–VI or III–V elements.⁸ The sizes of QDs normally range between 2 and 12 nm, which can be adjusted to modulate their optical properties. QDs have high extinction coefficients and high fluorescence quantum yields, which facilitate the development of QDs as fluorescent probes for detection and imaging.^9–12

Physical, chemical, and biological methods have been developed for the preparation of QDs. However, QDs synthesized by the first two methods have many drawbacks in biomedical applications, such as poor biocompatibility and low water solubility, making them difficult to use directly.¹³ QDs prepared by biosynthetic methods can overcome the shortcomings of QDs synthesized physically or chemically. Microorganisms have the ability to serve as “living factories” for synthesizing QDs under milder synthetic conditions. The microbial synthesis of QDs avoids the need for toxic substances by utilizing biomolecules to control and regulate the synthesis process. Additionally, QDs produced through microbial biosynthesis often possess distinct properties in comparison with chemically or physically synthesized QDs due to the presence of biomolecules such as proteins on their surfaces. Acidophilic bacteria, for instance, generate QDs with enhanced tolerance to lower pH levels when compared to QDs prepared using conventional methods. Due to the comprehensive genetic engineering toolbox of microbes, they have been widely explored for the biosynthesis of QDs. Microbially synthesized QDs have been investigated for various applications, such as antibacterial treatment,¹⁴ photocatalysis,¹⁵ and bioimaging.¹⁶ Furthermore, the QDs synthesized by microbes can assemble QD–microbe hybrids to integrate the optical and electronic properties of QDs and the biological properties of microbes.¹⁷ The microbial biosynthetic process of QDs can be influenced by a variety of extracellular and intracellular factors. Microbial culture conditions, such as temperature, pH, and precursor concentration, affect microbial cell growth and consequently influence the synthetic efficiency of QDs. The gene transcription and protein expression in microbial cells also regulate the biosynthesis of QDs.

In this review, we summarize the recently reported microbially synthesized QDs and their applications. Biosynthesized nanoparticles without reported QD properties are beyond the scope of this review. The regulation of the microbial synthesis of QDs by extracellular factors (e.g., pH) and intracellular factors (e.g., enzymes) is also discussed, which provides insights into improving the biosynthesis of QDs. Finally, we examine the limitations of QD biosynthesis that need to be overcome to better tailor the properties of QDs for new applications.

2. Microbial biosynthesis of quantum dots

In the early days of research on QDs, chemical synthesis was the main method used. In the early 1980s, Kalyanasundaram et al. synthesized CdS QDs under alkaline conditions utilizing (NH₄)₂S and CdSO₄ as the precursors.¹⁸ Their method required a long reaction time and harsh reaction conditions. Later, a variety of physical and chemical methods have been established to synthesize QDs in a top-down or bottom-up manner.¹⁹ Top-down synthesis involves disintegrating bulk materials into nanoscale particles using a variety of methods, such as chemical exfoliation²⁰ and mechanical exfoliation.²¹ Bottom-up methods assemble nanoparticles from fundamental building blocks, such as atoms and molecules, using methods including microwave synthesis,²² thermal decomposition,²³ and hydrothermal synthesis.²⁴ Due to the poor biocompatibility of the physically or chemically synthesized QDs, they need to undergo surface modification before being used for biological applications such as biomedical and bioimaging.^25–27

To overcome the shortcomings, synthetic methods for QDs using biological systems have been developed.^28–30 Dameron et al. first reported the biosynthesis of CdS QDs in fungi Candida glabrata and Schizosaccharomyces pombe.³¹ The fungi-biosynthesized QDs exhibited better monodispersity compared to those synthesized chemically. Since then, numerous microorganisms, including bacteria,³² fungi,^33,34 microalgae,³⁵ and viruses,³⁶ have been thoroughly investigated for QD biosynthesis.

It is the metal chelating and reducing activities of microbes that mainly contribute to their capability of biosynthesizing QDs.³¹ Microbes can also produce enzymes to decompose chemical substrates, generating precursors for QD synthesis. For example, Stenotrophomonas maltophilia expresses cystathionine gamma-lyase that converts cysteine to S²⁻ to form sulfide QDs in the presence of metal ions.³⁷ In addition, microorganisms, such as viruses, are often used as templates in the synthesis of QDs because of their biomolecule-decorated surfaces.³⁶ Some microbes, for example Escherichia coli and Saccharomyces cerevisiae, can proliferate and reproduce rapidly and can be conveniently genetically edited, which makes them more appealing than other species for QD biosynthesis. Microbially biosynthesized QDs usually feature biomolecular modification on their surfaces and are therefore more biocompatible. Table 1 summarizes the examples of microbially synthesized QDs and their key properties.

Table 1 Properties of microbially biosynthesized QDs

Organisms	Type	Localization	Size distribution (nm)	Excitation/emission (nm/nm)	Quantum yield	Ref.
— Means the data not reported in the literature.
Bacteria
Escherichia coli (wild-type/genetically engineered)	CdS	Intracellular	2–5	—/—	—	40
			6	350/445–510	—	46
			10	—/470	—	90
			2–6	320/384	0.00007	43
	CdSe	Intracellular	1.97 ± 0.02 or 5.49 ± 0.01 (affected by oxygen)	—/560, 430 (affected by oxygen)	—	99
			5.01 ± 0.89	—/—	—	44
	CdTe	Intracellular	2–3	—/488–551	0.15	16
			7.01 ± 0.66	—/—	—	44
	ZnO	Intracellular/extracellular	10.51 ± 1.71 (intracellular)/6.62 ± 0.35 (extracellular)	—/—	—	45
	Ag2S	Intracellular/extracellular	10.93 ± 1.94 (intracellular)/13.47 ± 1.21 (extracellular)	—/—	—	45
	SnO2	Intracellular/extracellular	5.17 ± 0.33 (intracellular)/7.72 ± 1.41 (extracellular)	—/—	—	45
	Cu2O	Intracellular/extracellular	17.69 ± 3.23 (intracellular)/4.90 ± 0.25 (extracellular)	—/—	—	45
	CdS : Ag	Extracellular	<15	—/—	0.3613	61
	CdZn	Intracellular	10.01 ± 0.97	—/—	—	44
	ZnSe	Intracellular	3.92 ± 0.35	—/—	—	44
	CdSxSe1−x	Intracellular	3.82 ± 0.53	—/—	—	113
	CdSe/CdS	—	3	295/350, 575		121
	AglnS2/In2S3	Extracellular	15–20	438/570	—	130
	CdSxSe1−x	Extracellular	2–5	420/550		131
Bacillus amyloliquefaciens	CdSe	Intracellular	3.57 ± 0.31	380/521–560	—	32
Stenotrophomonas maltophilia	CdS	Extracellular	2–4	312–378/460–562	0.73	37
	PbS	Extracellular	<8	—/1040–1135	0.16–0.45	125
Shewanella oneidensis	Ag2S	Extracellular	9 ± 3.5	410/—	—	49
	CdS	Extracellular	4.98–5.25 (affected by substrates)	255/395	—	57
Pseudomonas spp.	CdS	Extracellular	10–40	400/500–600	—	62
Acidithiobacillus sp.	CdS	Extracellular	6 or 10	360/460–650	—	97
Methanosarcina barkeri	CdS	Extracellular	10–100	—/—	—	132
Rhodopseudomonas palustris	CdS	Extracellular	<10	—/—	—	133
			<20	—/—	—	134
Fungi
Torulopsis sp.	PbS	Intracellular	2–5	—/—	—	67
Aspergillus sp.	PbS	Extracellular	10–15	—/—	—	79
Saccharomyces cerevisiae	ZnS	Intracellular	30–40	280/350, 440	—	68
				325/380, 440, 525
	Ag2Se	Extracellular	3.9 ± 0.6	400/920–1040	—	34
	CdSe	Intracellular	—	—/575	0.047	74
			3.0 ± 0.3	400/528	—	75
			—	—/—	—	136
			2.69–6.34	405/520, 560,670 (affected by the incubation time)	—	69
Aspergillus flavus	ZnS : Gd	Intracellular	10–18	315/—	—	122
Fusarium oxysporum	CdSe	Extracellular	11 ± 2	370/440	—	33
Other
Chlorella pyrenoidosa	CdSe	Intracellular	5–6	365/470	—	35
Scenedesmus obliquus	CdSe	Intracellular	5–6	365/480	—	35
Tobacco mosaic virus	CdS	Extracellular	5	—/—	—	36
	PbS		30
Phage M13	CsPbBr3	Extracellular	13.25 ± 2.69	—/—	0.401	83
	ZnS	Extracellular	3–5	—/—	—	82
	CdS		3–5	350/425	—

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2.1 Quantum dots biosynthesized by bacteria

Bacteria are unicellular prokaryotic organisms that generally have short growth and reproduction cycles. They have been explored for QD biosynthesis, and changes in their cultivation conditions can modulate the characteristics of the resulting QDs.^38,39 The transition metal sulfide QDs synthesized by bacteria are the most extensively studied types.³⁸ The sulfur in the QDs can be generated by bacteria or come from supplemented chemicals directly. In early investigations of the bacterial synthesis of QDs, Na₂S was supplemented to the bacterial culture to provide S²⁻ directly. CdS nanoparticles with a size range of 2–5 nm were synthesized by incubating E. coli with CdCl₂ and Na₂S.⁴⁰ The properties of the nanocrystals obtained at different E. coli growth stages varied substantially. More nanocrystals were synthesized in the stationary phase than in the late exponential phase. Although the quality of the E. coli synthesized QDs could not compete with that of QDs synthesized in glassware, this work identified the potential of bacteria to biosynthesize QDs and was a beginning for further optimizations.⁴¹

QD biosynthesis is commonly associated with the metal ion detoxification process that involves phytochelatins and metallothioneins. Phytochelatins and metallothioneins are ubiquitous biomolecules in living organisms, with phytochelatins being small peptides and metallothioneins being low molecular weight proteins. They play important roles in the detoxification of metals by forming complexes with metal ions.^31,42 Engineered E. coli capable of expressing phytochelatins was constructed to better produce CdS QDs with a size distribution of 2–6 nm (ref. 43) (Fig. 1A). Later, E. coli coexpressing phytochelatins and metallothioneins from a plasmid was constructed to synthesize various semiconducting nanoparticles⁴⁴ (Fig. 1B). In the presence of IPTG, which induces the expression of genes on the plasmid, phytochelatins and metallothioneins were produced to aid the biosynthesis of CdS QDs. The as-prepared QDs exhibited a fluorescence intensity four times higher than that of QDs synthesized by E. coli only expressing phytochelatins or metallothioneins alone. E. coli that coexpresses phytochelatins and metallothioneins has also demonstrated the ability to synthesize QDs such as Ag₂S, ZnO, etc.⁴⁵ Due to the genetic malleability of E. coli, it has been modified to express different components to modulate the QD biosynthetic process, including CdS-binding peptides, amyloid fibrils, arsenate reductase and thiosulfate reductase.^46–48

Fig. 1 Biosynthesis of quantum dots by different microbes. (A) E. coli strains were genetically engineered to improve the production of phytochelatins (PCs), leading to the enhanced biosynthesis of CdS QDs. SpPCS is the PC synthase from S. pombe; GSHI* is a feedback-desensitized γ-glutamylcysteine synthetase.⁴³ Copyright 2008 Wiley. (B) TEM images of various QDs synthesized by recombinant E. coli cells coexpressing the Phytochelatin synthase from Arabidopsis thaliana and the metallothionein from Pseudomonas putida. (a) CdZn, (b) CdSe, (c) CdTe, and (d) SeZn.⁴⁴ Copyright 2010 Wiley. (C) Biosynthesis of CdS : Ag QDs by E. coli. (a) Scheme of the formation of ternary CdS : Ag QDs by cation exchange. (b) Fluorescence of CdS : Ag QDs biosynthesized with different concentrations of AgNO₃.⁶¹ (D) Fluorescence of S. cerevisiae cells with engineered Se metabolism after the biosynthesis of CdSe QDs.⁷⁵ Scale bar = 5 μm. Copyright 2017 Springer Nature. (E) Synthesis of CsPbBr₃ using the M13 phage as the template. The M13 phage was genetically engineered to display more negatively charged amino acids.⁸³ Copyright 2020 Elsevier.

Besides E. coli, many other bacteria have been reported to biosynthesize QDs. Sulfur-containing chemicals including thiosulfates,⁴⁹ sulfates,⁵⁰ and cysteines³⁷ can be metabolized by bacteria to generate S²⁻ for metal sulfide QD synthesis. S. oneidensis, for example, can utilize extracellular thiosulfates as electron acceptors for anaerobic respiration, producing H₂S as the reduced product.⁵¹ The biosynthesized H₂S can form QDs with metal ions existing in the culture solution.^52–55 When incubated with AgNO₃ and Na₂S₂O₃, S. oneidensis can biosynthesize Ag₂S QDs with peptides coated on the surface.⁴⁹ The size of the QDs ranged from 7 to 9 nm, which was affected by substrate concentrations, temperature, and incubation time.⁵⁶ Changes in the reaction conditions also altered the synthetic efficiency. The maximum QD synthetic efficiency of 54% was achieved when cells were incubated at 24 °C for 96 hours with a 1 : 1 ratio of AgNO₃ and Na₂S₂O₃. The compositions of culture media also have effects on the bacterial biosynthesis of QDs.⁵⁷ The biosynthesis of CdS QDs by S. oneidensis was attempted in media with different components, suggesting that yeast extract was required for the biosynthesis. QDs were biosynthesized in the hexagonal phase exhibiting a high photocatalytic activity when yeast extract and peptone were supplemented at 6%, while at other ratios they were mainly in the cubic phase. The culture media need to be formulated carefully to support the growth of S. oneidensis cells without inducing too rapid growth which suppresses the conversion from cysteine to H₂S.

Besides metal sulfide, bacteria are capable of biosynthesizing other types of QDs. Bacillus subtilis was incubated with K₂TiF₆ solution for 48 hours to synthesize TiO₂.⁵⁸ The B. subtilis cells acted as templates to promote the formation of TiO₂. The prepared TiO₂ QDs exhibited antibacterial activities under irradiation by generating cytotoxic hydroxyl radicals. In the chemical synthesis of QDs, the cation exchange technique has been commonly applied to achieve doping.^59,60 A similar technique has been explored in the biosynthesis of ternary or quaternary QDs by bacteria.⁶¹ By adding AgNO₃ to the culture of E. coli biosynthesizing CdS QDs, Ag⁺ in the solution could gradually replace Cd²⁺ in the CdS, slowly transforming CdS to CdS : Ag and Ag₂S QDs (Fig. 1C). The CdS : Ag QDs exhibited fluorescence and photovoltaic properties and could be used in biological applications and quantum dot sensitized solar cells.

In summary, bacteria have the capability of biosynthesizing QDs including the most studied CdS and ternary or quaternary QDs. E. coli and S. oneidensis are the commonly used species, but other exotic bacteria such as extremophilic bacteria have also been explored for QD biosynthesis.⁶² Bacterial biosynthesis of QDs uses milder reaction conditions and enables surface modification with biomolecules for biological applications.¹⁶

2.2 Quantum dots biosynthesized by fungi

In contrast to bacteria, fungi are multicellular or unicellular eukaryotic microbes. Most of the fungi used for QD biosynthesis are unicellular. Fungi can secrete proteins to promote the reduction of metal ions or to serve as metal-binding agents. The secreted proteins can be stabilizers for nanoparticles, thereby improving the biosynthesis of nanoparticles.^63–65 The preparation of nanomaterials by fungi can be easily scaled up by increasing the culture volumes.^63,66

C. glabrata or S. pombe can produce metal chelating peptides to bind Cd²⁺ and facilitate the formation of CdS QDs with a size of approximately 2 nm in the presence of Na₂S.³¹ This observation inspired attempts to biosynthesize other QDs using fungi, for example PbS⁶⁷ and ZnS⁶⁸ QDs. As a model fungus, S. cerevisiae has been extensively studied for QD biosynthesis. The Na₂SeO₃ metabolic reactions were coupled with the Cd²⁺ detoxification process in S. cerevisiae to biosynthesize CdSe QDs.⁶⁹S. cerevisiae was incubated with Na₂SeO₃ during the stationary phase to achieve seleniumized cells and then supplemented with Cd²⁺. The extended co-incubation time with Cd²⁺ resulted in a change in the size of QDs from 2.69 nm to 6.34 nm, along with a change in the fluorescence emission from green to red. Glutathione (L-γ-glutamyl-L-cysteinylglycine, GSH) is a ubiquitous tripeptide that is involved in many cellular activities including the detoxification of metal ions.^70–73 The GSH metabolism in S. cerevisiae was modulated using genetic tools to tune the biosynthesis of CdSe QDs.⁷⁴ Increasing the GSH content by upregulating the genes responsible for GSH synthesis significantly enhanced the production yield of CdSe QDs. In addition to GSH metabolism, engineering the Se/S metabolic pathway is an alternative strategy to modulate the biosynthesis of QDs⁷⁵ (Fig. 1D).

In addition to S. cerevisiae, other non-model fungi have also been reported to possess QD biosynthetic capabilities.⁷⁶Fusarium oxysporum can mediate the synthesis of CdSe QDs at room temperature in a solution containing CdCl₂ and SeCl₄.³³ The resulting QDs were spherical in shape with a size of 11 ± 2 nm, exhibiting intense emission at 440 nm when excited by 370 nm light. Further investigation of this biosystem unveiled that superoxide is accumulated during the biosynthesis of CdSe, which may increase the expression of other metabolites that mediate the reduction of Se⁴⁺ and inhibit the aggregation of CdSe.^77,78 An Aspergillus sp. isolated from the rhizosphere of chickpea was used to synthesize spherical PbS QDs with sizes of 10–15 nm.⁷⁹ Recently, Au₂S QDs have been successfully biosynthesized using a Humicola sp.⁸⁰ Fungi are promising workhorses to biosynthesize QDs, but the understanding of the synthetic mechanisms in fungal systems is still very limited.

2.3 Quantum dots synthesized by viruses

Because viruses have no intact cellular structures and cannot synthesize or secrete proteins independently like bacteria or fungi, they typically act as biological templates to promote the synthesis of QDs.⁸¹ Although here we discuss the synthesis of QDs by viruses, we need to clarify that viruses do not mediate biological reactions to induce the synthesis of QDs. “Biosynthesis” by viruses is actually the synthesis of QDs that occur on the biological components of viruses.

Tobacco mosaic virus (TMV) is a well-studied model virus that has a large number of protein subunits containing many charged amino acid residues on the surfaces, which provide nucleation sites for QD formation. When exposed to H₂S gas for several hours in the presence of TMV, CdCl₂ and Pb(NO₃)₂ turned into 5 nm CdS and 30 nm PbS QDs.³⁶ As the protein shell of viruses plays an important role in the synthesis of QDs, attempts have been made to engineer the protein shell for the optimization of QD synthesis. The M13 phage was genetically modified to express peptides that promote the nucleation and growth of CdS and ZnS QDs.⁸² When peptides were present on the phage, nanocrystals could nucleate and form a nanowire structure. The amino acid composition of the expressed peptides had a significant impact on the structure and nucleation density of the biosynthesized nanocrystals. With the phage expressing the CNNPMHQNC peptide, the formed ZnS exhibited a wurtzite structure with 8–16 QDs per 10 nm of the virus, whereas the ZnS formed on the surface of viruses expressing the VISNHAESRRL peptide had a zinc blende structure with only 1.6–3.2 QDs per 10 nm of the virus.

Interestingly, viruses have been applied to synthesize QDs that cannot be biosynthesized by bacteria or fungi. Lee et al. reported that a genetically engineered M13 phage with increased negative charges could assist in the synthesis of CsPbBr₃ perovskite QDs⁸³ (Fig. 1E). The charge on the phage surface stabilized the perovskite QDs, enabling them to retain the photoluminescence for 30 days. The phage–QD hybrids exhibited a substantially higher photoluminescence quantum yield of 40.1%, which was 2.99 times higher than that of CsPbBr₃ synthesized conventionally without the M13 phage. The formation of hybrids of QDs and microbes is an appealing strategy to improve the performance of QDs.

2.4 Quantum dots biosynthesized by other organisms

Bacteria, fungi, and viruses are the most investigated microorganisms for the synthesis of QDs, while other microorganisms have been rarely studied despite their potential to biosynthesize QDs. Microalgal cells (e.g., Chlorella pyrenoidosa and Scenedesmus obliquus) can produce GSH to reduce Na₂SeO₃ and form CdSe QDs intracellularly in the presence of Cd²⁺.³⁵ The as-synthesized QDs were used to develop fluorescent probes for the detection of imatinib. The biosynthesis of CdSe QDs was reported in protozoa as well. Tetrahymena pyriformis biosynthesized CdSe QDs when incubated with Na₂SeO₃ and CdCl₂.⁸⁴ However, due to the sensitivity of protozoa to the external environment, applications involving protozoa are not robust and therefore studies on the biosynthesis of QDs by protozoa are limited.

In addition, other living systems, ranging from mammalian cells to living animals, can also synthesize QDs.^29,85,86 When challenged by heavy metals, these biosystems harness biomolecules (e.g., GSH and metallothioneins) to detoxify the metal ions and thus biosynthesize QDs in the presence of suitable anions.

3. Regulation of quantum dot biosynthesis

The biosynthesis of QDs assists microbes in enhancing their adaptation to their habitats, for example, by detoxifying heavy metals. Microbes utilize biomolecules such as proteins to chelate metal ions while also producing enzymes that generate substrates like H₂S to facilitate the synthesis of QDs. Taking the synthesis of CdS QDs by E. coli as an example, E. coli produces cysteine desulfhydrase that breaks down cysteine into H₂S. The resulting H₂S reacts with Cd²⁺, ultimately forming CdS QDs⁶¹(Fig. 2A). Compared to bacteria, the process of QD synthesis in fungi is more intricate. Currently, most of the research on fungal QD synthesis has been conducted in S. cerevisiae. During the process of CdSe QD synthesis in S. cerevisiae, the substrate SeO₃²⁻ undergoes a transformation into selenomethionine (SeMet) form catalyzed by the enzyme MET6. Simultaneously, the presence of Cd²⁺ induces the production of enzymes that are involved in the conversion of SeMet to selenocysteine (SeCys). Finally, the resulting SeCys interacts with GSH-detoxified Cd²⁺ to form CdSe QDs⁷⁵ (Fig. 2B).

Fig. 2 Representative schemes of quantum dot biosynthesis in bacteria and fungi. (A) Biosynthesis of CdS QDs by Escherichia coli.⁶¹ (B) Biosynthesis of CdSe QDs in engineered S. cerevisiae overexpressing MET6. MET6 catalyzes the transformation from SeO₃²⁻ to SeMet. The enzymes SAM1, SAM2, SAH1, CYS4, and CYS3 are responsible for the conversion from SeMet to SeCys.⁷⁵Copyright 2018 Springer Nature.

The physical properties of QDs (e.g., size, shape, and crystallinity) have impacts on their optical properties, which affect the performance of QDs in applications. For example, the 3.66 nm SnS QDs outperform the 7.14 nm ones in photocatalytic activity and photovoltaic performance.⁸⁷ Therefore, it is crucial to regulate and optimize the biosynthetic process of QDs to modulate their properties.⁸⁸ The microbial biosynthesis of QDs is influenced by external factors such as temperature, pH, and substrate types and concentrations. Intracellular components including metabolites and proteins also contribute to the regulation of QD biosynthesis (Fig. 3).

Fig. 3 Key processes and factors involved in the regulation of the microbial biosynthesis of QDs (taking CdS QDs as an example). (Green arrows represent processes that benefit the formation of QDs; red arrows represent processes that need to be suppressed to enhance the formation of QDs.).

3.1 Regulation by extracellular factors

Extracellular factors, such as medium compositions, precursor concentrations, temperature, and pH, affect the growth of microbial cells, thereby influencing the microbial biosynthesis of QDs. These factors need to be adjusted to maintain the growth of microbial cells at an appropriate rate, without inhibiting the biological pathways involved in QD biosynthesis. The concentration of precursors is a crucial factor in the QD synthesis process. A low precursor concentration leads to low QD synthetic efficiency, whereas a high precursor concentration may result in decreased microbial cell activities.

During the biosynthesis of CdSe QDs by S. cerevisiae, it was found that the high concentrations of Cd (5 mM) inhibited the enzymatic activity and cell growth of S. cerevisiae, thus reducing the efficiency of QD synthesis. Meanwhile, the oxidative stress caused by reactive oxygen species generated at a high concentration of Na₂SeO₃ (7 mM) also led to a decrease in cell viability and hindered the synthesis of CdSe QDs.⁸⁹ It is critical to optimize the concentrations of all the precursors to ensure the survival of microbes and to maximize the synthetic efficiency. The changes in the concentration of precursors also modulate the optical properties of biosynthesized QDs. E. coli expressing binding peptides for CdS was capable of biosynthesizing QDs with Cd²⁺ and S²⁻ in the range of 0.5–10 mM.⁴⁶ The increase in reactant concentrations increased the sizes of QDs and led to a redshift in the emission. The different time points of precursor supplementation and the varied incubation duration with microbial cells result in different biosynthesis outcomes. E. coli cells at the stationary stage had a greater ability to synthesize CdS QDs than cells at the early and exponential growth stages.⁹⁰ If the incubation time is longer than 5 days, the activity of the E. coli cells decreases, resulting in a decrease in the yield of QDs.

Different strains have varying levels of tolerance to different precursor chemicals, and therefore strategies have been developed to select tolerant strains or develop resistant strains via continuous mutagenesis and screening. For instance, a cadmium-tolerant Stenotrophomonas maltophilia strain was selected and isolated from LB media containing increasing concentrations of cadmium acetate (0.1–5 mM).³⁷ The isolated S. maltophilia exhibited high resistance to Cd and was successfully applied to biosynthesize CdS QDs.

Most of the studies on the microbial biosynthesis of QDs provided a single type of metal ion to microbial cells. When different metals were provided, ternary or quaternary QDs could be biosynthesized. A consortium of sulfate-reducing bacteria containing Desulfovibrio, Clostridiaceae, Proteiniphilum, Geotoga, and Sphaerochaeta were applied to biosynthesize ternary QDs by providing different ratios of Zn²⁺ and Cd²⁺.^91,92 Addition of Zn²⁺ to the mixture for the biosynthesis of CdS QDs resulted in doping the QDs with Zn²⁺, which attenuated the toxicity and improved the biocompatibility and stability of CdS QDs while retaining the fluorescence properties. Ternary QDs with tunable fluorescence properties and low toxicity were achieved via changing the ratios of Zn²⁺ and Cd²⁺, which showed great potential for biomedical applications.^92–95

Other factors including temperature and pH are known to affect cellular metabolism, thus influencing the biosynthesis of QDs by microbes.⁹⁶ For example, in the biosynthesis of CdS QDs using P. chlororaphis extracts, the reaction conditions were optimized to achieve QDs with optimal absorption at 30 °C and a pH of 7.5. Extremophilic microbes have been explored for QD biosynthesis due to their tolerance to extreme temperatures or pH. An oxidative stress-resistant Antarctic Pseudomonas strain was isolated, which is capable of biosynthesizing CdS QDs efficiently at 15 °C, a temperature that greatly reduces the QD biosynthetic efficiency in other microbes.⁶² The low temperature conditions contributed to more nucleation sites for QD synthesis, resulting in better control of the size and dispersion of the synthesized QDs. Biosynthesis of CdS QDs at low pH was accomplished by using acidophilic bacteria, belonging to the Acidithiobacillus genus, that are tolerant to acidic conditions.⁹⁷ The QDs were biosynthesized at pH = 2.0, which retained good fluorescence properties due to the protection provided by biomolecules secreted by the bacterium (Fig. 4A). QDs synthesized by acidophilic bacteria overcome the challenges associated with fluorescence quenching at a low pH, which is a common problem for QDs synthesized by other microbes, and enable the applications of biosynthesized QDs under acidic conditions.⁹⁸ Phosphate was reported to have an effect on the biosynthesis of QDs by Acidithiobacillus. An increase in phosphate concentration improves the cadmium uptake and tolerance of the bacteria, thus enhancing the production of CdS QDs.

Fig. 4 Effects of different microbes and their growth conditions on the properties of biosynthesized QDs. (A) The pH tolerance of CdS QDs produced by chemical synthesis, E. coli and A. thiooxidans cells. The effect of pH on the fluorescence emission spectra of these QDs was evaluated after 40 min exposure to different pH conditions. The fluorescence intensity of QDs biosynthesized by A. thiooxidans was less influenced by lower pH compared to QDs chemically synthesized or those biosynthesized by E. coli. (Red and green CdS QDs were synthesized by A. thiooxidans with different incubation times.).⁹⁷ Copyright 2016 Elsevier. (B) Biosynthesis of CdSe QDs by E. coli under anaerobic and aerobic conditions. (a) Optical and fluorescence images and (b) changes in the fluorescence intensities of the E. coli suspension during the QD biosynthetic process. The CdSe QDs synthesized by E. coli under anaerobic conditions exhibited stronger fluorescence intensities.⁹⁹ Copyright 2022 The Royal Society of Chemistry.

The oxygen level is a factor that can affect the accumulation of intracellular ROS, thereby impairing the metabolism of microbial cells and their capability to biosynthesize QDs.⁹⁹ Under anaerobic conditions, E. coli cells accumulated less ROS under exposure to Cd and Se contents and exhibited better efficiency for CdSe QD biosynthesis compared to that of aerobic culture (Fig. 4B). In addition, the levels of GSH and NADPH were elevated in anaerobically cultivated E. coli cells, which also contributed to the biosynthesis of CdSe QDs via mediating the reduction of SeO₃²⁻.

3.2 Regulation by intracellular components

Microorganisms have sophisticated metabolic networks involving complex metabolites, both small molecules and macromolecules, that have impacts on the biosynthesis of QDs. The microbial biosynthesis of QDs normally involves the stress defense mechanism to deal with heavy metals, including biomineralization and other biological detoxification processes.^100,101 To resist the toxic effects of metal ions, some microbes produce biomolecules to bind metal ions. The complexes of metal ions and biomolecules can reduce the toxicity of metals and can be engaged in the biosynthesis of QDs.^102–104 The peptide phytochelatin and protein metallothionein are ubiquitous and well-studied biomolecules capable of binding heavy metals for biodetoxification.¹⁰⁵ Overexpression of phytochelatins or metallothioneins in microbial cells can improve the utilization of metal ions, thereby enhancing their ability to synthesize QDs. It was demonstrated that during the biosynthesis of CdS QDs by C. glabrata and S. pombe, phytochelatins were produced and used as both templates and stabilizers to promote the formation of CdS.³¹ Coexpression of the Phytochelatin synthase from Arabidopsis thaliana and the metallothionein from Pseudomonas putida enabled E. coli cells to biosynthesize QDs using a wide range of metals, including semiconducting (Cd, Se, Zn, and Te), alkali-earth (Cs and Sr), magnetic (Fe, Co, Ni, and Mn), noble (Au and Ag), and rare-earth (Pr and Gd) metals. Overexpression of the two biomolecules increased the efficiency of QD synthesis. E. coli cells containing the coexpression system produced QDs emitting fluorescence four-fold stronger than that of E. coli overexpressing phytochelatins alone.⁴⁴

In addition to Phytochelatin synthase, overexpression of enzymes that generate precursors for Phytochelatin biogenesis also contributed to improved QD synthesis by microbes. GSH is the substrate for Phytochelatin biogenesis, and therefore accumulation of GSH leads to more Phytochelatins. An engineered E. coli strain was constructed containing a plasmid encoding γ-glutamylcysteine synthetase, which can catalyze the synthesis of GSH. This engineered strain produced phytochelatins ten times more than the wild-type strain, resulting in significantly improved biosynthesis of CdS QDs. This strategy was also applied to E. coli R189, a strain naturally not capable of producing CdS, to generate CdS QDs efficiently.⁴³ Besides being a precursor of Phytochelatin biosynthesis, GSH plays an important role in maintaining cellular redox homeostasis. GSH is involved in many intracellular biological pathways.¹⁰⁶ In earlier works using S. cerevisiae to synthesize CdSe QDs, it was highlighted that GSH and GSH-related enzymes are required for the reduction of selenium.^52,69 Likewise, in the case of biosynthesizing CdTe with E. coli, GSH was also required and the overexpression of genes responsible for the synthesis of GSH significantly increased the efficiency of QD synthesis.¹⁰⁷

Further studies investigated the effects of genes involved in the biosynthesis of GSH on QD synthesis in detail.⁷⁴ In S. cerevisiae, the genes GSH1, GSH2, and GLR1 encode γ-glutamylcysteine ligase, glutathione synthetase and glutathione reductase, respectively. They are critical genes in the GSH metabolic pathway. The relevance of these genes to QD biosynthesis was investigated by using deletion mutant strains to synthesize CdSe QDs. Deletion of any of the three genes led to a reduction in the intracellular fluorescence intensity of the synthesized QDs, indicating that each gene is essential for the biosynthesis of QDs. The expression of GSH-related enzymes was regulated during the QD synthetic process. After the addition of Cd to S. cerevisiae cells that had been incubated with Na₂SeO₃, the GSH1 gene was significantly upregulated. S. cerevisiae was further genetically engineered to regulate the GSH1 gene for optimization of QD synthesis. A plasmid containing the GSH1 gene was introduced into S. cerevisiae, resulting in the overexpression of GSH1, which enhanced the yield of CdTe QDs by nearly four-fold. Recent studies have found that the biosynthesis of QDs in microalgae is also associated with GSH. The GSH content in microalgal cells increased continuously with the addition of Na₂SeO₃ in the absence of Cd²⁺. After Cd²⁺ was supplemented, the GSH content in cells dropped gradually as the CdSe QDs started to be synthesized.³⁵

Besides GSH-related enzymes, other microbial enzymes, such as enzymes involved in H₂S metabolism, have an influence on QD biosynthesis as well. For instance, S. maltophilia biosynthesizes CdS QDs efficiently due to its expression of cystathionine γ-lyase that catalyzes the biogenesis of H₂S from cysteine.^37,108 Genes involved in the sulfate assimilation pathway have been investigated in S. cerevisiae and regulation of these genes can control the abundance of H₂S in cells.¹⁰⁹ By deleting genes MET17 or CYS4 that mediate the conversion of H₂S to thiol-containing amino acids, significantly more H₂S could be produced by S. cerevisiae.¹¹⁰ As H₂S can be used by microbial cells to biosynthesize sulfide QDs, overexpressing synthetic genes for H₂S or downregulating genes that consume H₂S are promising strategies to enhance the biosynthesis of sulfide QDs (Fig. 5A).

Fig. 5 Regulation of QD biosynthesis by intracellular components. (A) The metabolic pathways related to H₂S biogenesis and transformation in S. cerevisiae. (a) Knockout of the genes highlighted in red enhances the production of H₂S. (b) The glycine–cysteine peptide motifs displayed by S. cerevisiae cells improve the crystallinity of biosynthesized CdS QDs. With more crystalline features, the QDs exhibited stronger fluorescence emission. Displayed peptide motifs: 1, GGGGGG; 2, CCCCCC; 3, GGCGGC; 4, GCCGCC.¹¹⁰ Copyright 2020 Springer Nature. (B) Accumulation of intracellular Cd²⁺ in E. coli contributes to improved production of CdSe QDs. (a) Knockout of the zntA gene, which blocks the efflux of Cd ions, accumulates intracellular Cd²⁺ for the biosynthesis of QDs. (b) The engineered strains with zntA deletion exhibit more intense fluorescence emission after the biosynthesis of QDs compared to the wild-type and complemented strains.¹¹³ Copyright 2021 Elsevier.

In the case of the biosynthesis of selenium QDs, enzymes participating in the metabolism of Se were studied. It was demonstrated that selenocysteine is the major selenium precursor for the biosynthesis of CdSe QDs. The metabolic flux between selenohomocysteine, selenomethionine, and selenocysteine regulates the biosynthesis of selenium QDs in S. cerevisiae. Engineering the selenium metabolism via overexpressing the MET6 gene in S. cerevisiae achieved a more than three-fold increase in the CdSe QD yield.⁷⁵ Likewise, selenocysteine also plays an important role in the biosynthesis of Ag₂Se. Overexpression of the gene MET6 in S. cerevisiae enhanced the fluorescence intensity of the synthesized Ag₂Se QDs four times. The resulting Ag₂Se QDs had a size of 3.9 nm, a maximum emission wavelength in the NIR-II region (1040 nm), and could be applied to bioimaging in the NIR-II window.³⁴

The access of microbial cells to metal ions affects the biosynthesis of QDs. E. coli is Cd tolerant due to the Cd ion efflux activity of the ZntA protein.^111,112 The ZntA protein limits the intracellular concentration of Cd²⁺, thus hindering the biosynthesis of QDs. By knocking out the zntA gene, the efflux of Cd ions can be blocked, accumulating more intracellular Cd²⁺ for the synthesis of QDs. Compared to the wild-type E. coli cells, the synthetic efficiency of CdS_xSe_1−x QDs in E. coli cells without the ZntA protein was increased by 50% (ref. 113) (Fig. 5B).

In addition to regulating the intrinsic metabolites and proteins, introduction of exogenous peptides into microbes has been explored as a strategy to facilitate the biosynthesis of QDs. For example, CdS-binding peptides were heterologously expressed in engineered E. coli cells to cap and stabilize biosynthesized CdS QDs.⁴⁶ Chen et al. designed an E. coli strain that can produce amyloid fibrils displaying ZnS-nucleation peptides.⁴⁷ The cells expressing the peptides nucleated 5 nm ZnS QDs which exhibited a zinc blende structure, whereas fewer such nanoparticles were biomineralized by control cells not displaying the ZnS-nucleation peptides. Similarly, for S. cerevisiae, different nucleating peptides displayed on the surface can modulate the crystalline structures of the biosynthesized CdS QDs¹¹⁰ (Fig. 5A).

The regulation of QD biosynthesis by intracellular components occurs mainly through modifying the accessibility of precursor substrates, mediating intracellular redox homeostasis, and stabilizing QDs. Understanding the mechanism of QD biosynthesis in microorganisms in more detail will help design new strategies to regulate their synthesis and tune their properties.

4. Application

The microbial biosynthesis of QDs can be performed under mild conditions and can be scaled up by expanding the culture volumes. Biosynthesized QDs are generally capped with biomolecules and are thus more biocompatible than chemically synthesized QDs. This section will discuss the modification and applications of QDs biosynthesized by microbes and the applications of QD–microbe hybrids as well.

4.1 Application of quantum dots biosynthesized by microbes

Most physically or chemically synthesized QDs exhibit low water solubility and require additional modifications to improve their biocompatibility.¹¹⁴ Incorporating biomolecules onto the surface of QDs is a common technique for enhancing the biocompatibility of QDs.^115,116 The QDs biosynthesized by microbes naturally have proteins and peptides attached to their surfaces, and therefore they are more water soluble and can be further modified more easily. The protection provided by surface biomolecules helps biosynthesized QDs adapt to applications under different conditions. For example, CdS QDs synthesized by E. coli cells have better acidic pH tolerance than chemically synthesized QDs. The fluorescence intensity of the chemically synthesized QDs decreased significantly at pH = 6, whereas the fluorescence of the QDs synthesized using E. coli remained intact. When acidophilic bacteria were used, the fluorescence of the biosynthesized QDs was not significantly affected even when the pH was lowered to 2.⁹⁷ Such acid tolerant QDs can be potentially used under extreme conditions, for instance, biomedical applications in the gastrointestinal tract.⁹⁸ Biosynthesized QDs without additional modifications have been directly applied in sensing, bioimaging and energy storage.^32,34,61

4.1.1 Nanosensors. Due to the exceptional physical and optical properties of QDs, an increasing number of studies have explored their applications as nano-sensors.¹¹⁷ Biosensors based on QDs have been developed to detect a variety of biomolecules including proteins, DNA, and microRNA.^118,119 For example, recently Wang et al. developed a QD-based FRET nanosensor that can accurately quantify miRNA-155 at the single-cell level. This sensor was used to distinguish samples from healthy persons and nonsmall cell lung cancer patients.¹²⁰ QDs biosynthesized by microbes have been developed into nanosensors as well. The surface proteins on the biosynthesized QDs can be utilized to easily modify the nanomaterial for optimized performance in certain applications. The CdSe/CdS QDs biosynthesized by E. coli were modified for Hg²⁺ detection¹²¹ (Fig. 6A). The QDs were conveniently modified with the amino-modified DNA probe P3 using the carboxyl groups from the surface proteins. Liposomes were attached to DNA probes P2 that contain two DNA segments. When Hg²⁺ is present, one of the two segments forms a complex with DNA probe P1 fixed on a slide. The segment from P2 and the probe P1 are rich in thymine, which can form thymine–Hg²⁺–thymine base pairs. The other segment from P2 could bind P3-QDs to elicit a fluorescence response. As one liposome could bind more than one QD, this analytical system enabled signal amplification and could detect Hg²⁺ at concentrations as low as 0.01 nM. This sensor took advantage of the ease of functionalization and the great biocompatibility of the biosynthesized QDs. The properties of the biosynthesized QDs can also be modified by doping with other metal elements via supplementing microbes with additional metals during their cultivation. Gadolinium-doped ZnS QDs were biosynthesized by Aspergillus flavus with gadolinium nitrate supplied in addition to the Zn precursors.¹²² The luminescence of Gd-doped ZnS QDs was substantially quenched in the presence of Hg²⁺ or Cu²⁺, making them suitable for heavy metal detection.

Fig. 6 Application of quantum dots biosynthesized by microbes. (A) The CdSe/CdS QDs biosynthesized by E. coli were modified with DNA sequences for Hg²⁺ detection. P1, P2, and P3 are DNA probes. The segment from P2 and the probe P1 are rich in thymine, which can form thymine–Hg²⁺–thymine base pairs. The other segment from P2 binds P3-QDs to elicit a fluorescence response.¹²¹ Copyright 2020 American Chemical Society. (B) Use of biosynthesized CdS : Ag QDs for fluorescence labeling of HeLa cells. HeLa cells transfected with a transfection agent and CdS : Ag QDs exhibited strong fluorescence.⁶¹ (C) The PbS@CdS QDs biosynthesized by S. maltophilia were applied to quantum dot sensitized solar cells, enhancing the open circuit potential and current density compared to the solar cells using PbS QDs without shells.¹²⁵ Copyright 2016 The Royal Society of Chemistry.

4.1.2 Bioimaging. QDs synthesized by microbes exhibit enhanced biocompatibility and have gained attention in the field of bioimaging. In a study conducted by Bao et al., well-crystallized CdTe QDs synthesized by E. coli were utilized for imaging of HeLa cells.¹⁶ Their results indicated that cells remained viable in the presence of 2 μM of CdTe QDs due to the surface protein capping layer. Upon being further modified with folic acid, the biosynthesized CdTe QDs could effectively label HeLa cells and be used for in vivo imaging. Moreover, doping with additional metal ions during the biosynthesis of QDs leads to the production of multi-component QDs, which can have enhanced performance in bioimaging applications. Biosynthesis of CdS : Ag QDs with near-infrared fluorescence (700–800 nm) was achieved in E. coli using the cation exchange method. The Ag-doped QDs were used to label HeLa cells exhibiting a high level of red signals⁶¹ (Fig. 6B). Compared to the fluorescence of NIR-I (700–950 nm), NIR-II fluorescence (1000–1400 nm) offers a higher signal-to-noise ratio, enabling imaging in deep tissues.^123,124 Recently, Liu et al. prepared Ag₂Se QDs with NIR-II emission (920–1040 nm) using S. cerevisiae.³⁴ The biosynthesised Ag₂Se QDs exhibited excellent biocompatibility, as evidenced by the sustained viability of cells at a high QD concentration of 500 μg mL⁻¹. The intravenously injected Ag₂Se QDs exhibited a remarkably strong fluorescence signal at the spleen location after four hours.

4.1.3 Energy storage. QDs synthesized by microorganisms also exhibit promising applications in the field of energy storage. In the application of quantum dot sensitized solar cells, the biosynthesized QDs doped with other elements also outperformed the ones without doping. By supplying AgNO₃ to the culture mixture of E. coli biosynthesizing CdS QDs, doping with Ag was achieved.⁶¹ The solar cells prepared from the as-synthesized ternary QDs were four times more efficient than those sensitized by Ag₂S alone and eight times more efficient than those sensitized only by CdS. QDs with a core–shell structure were biosynthesized by S. maltophilia via a two-step procedure.¹²⁵ Lead acetate and cysteine were provided to S. maltophilia for the biosynthesis of PbS QDs. Following the biosynthesis of the core, cadmium acetate was supplemented to biosynthesize the CdS shell. The obtained core–shell ternary QDs were applied to quantum dot sensitized solar cells, enhancing the open circuit potential and current density compared to the solar cells using PbS QDs without shells (Fig. 6C).

4.2 Application of quantum dot–microbe hybrids

4.2.1 Biosensors. In the above-mentioned applications, the biosynthesized QDs, either intracellularly or extracellularly synthesized, were isolated from microbial cells and purified after the synthesis. Recently, the self-assembled biohybrids of QDs and microbes have been applied directly without isolation of the biosynthesized QDs. For example, S. aureus biosynthesized CdSe QDs intracellularly, resulting in biohybrids with fluorescence. Protein A expressed on the surface of S. aureus could noncovalently interact with the Fc region of monoclonal antibodies to form biohybrid–antibody complexes.¹²⁶ Such complexes were used as biosensors to detect ultralow levels of prostate-specific antigen, demonstrating their potential for selective immunoassay of cancer biomarkers (Fig. 7A). Biohybrid biosensors of these kinds have better biocompatibility while incorporating the benefits of both QDs and living organisms.

Fig. 7 Application of quantum dot–microbe biohybrids. (A) S. aureus biosynthesized CdSe QDs intracellularly forming fluorescent biohybrids. Protein A expressed on the surface of S. aureus could noncovalently interact with the Fc region of monoclonal antibodies to form biohybrid–antibody complexes, which can be used as biosensors to detect ultralow levels of prostate-specific antigen.¹²⁶ Copyright 2019 American Chemical Society. (B) E. coli cells assembled with AglnS₂/In₂S₃ can accept electrons from photoexcited AglnS₂/In₂S₃. The intracellular electron transport efficiency of E. coli cells was promoted to enhance the production of H₂.¹³⁰ Copyright 2018 Elsevier. (C) CdS QDs assembled on M. barkeri cells generated photoexcited electrons that could be used to catalyze the reduction of ferredoxin involved in methanogenesis. Compared to wild-type M. barkeri cells, the production of CH₄ by the biohybrids was substantially improved.¹³² Copyright 2019 Elsevier. (D) The proposed mechanism for the enhanced N₂ fixation and biomass conversion in CdS-coated R. palustris. The photoexcited electrons of CdS QDs are passed to nitrogenase and NADP⁺via the PET chain. The fixation of atmospheric N₂ and the photosynthetic efficiency are promoted. (PS: photosystem, PET chain: photosynthetic electron transfer chain, Fd: ferredoxin, FNR: ferredoxin-NADP⁺ oxidoreductase, Cys: cysteine, CySS: cystine).¹³⁴ Copyright 2019 The Royal Society of Chemistry.

4.2.2 Clean energy production. QDs are semiconducting nanoparticles that can harvest energy from light to produce electrons to fuel biochemical reactions within microbial cells.^127,128 Under anaerobic conditions, E. coli can produce an endogenous hydrogenase that can be used to produce H₂, and the efficiency of this hydrogenase can be improved by semiconducting nanoparticles.¹²⁹ The hydrogenases were anchored on TiO₂ nanoparticles modified with carbon nitride to achieve increased visible light absorption and higher photoactivity. The electrons from photoexcited TiO₂ nanoparticles were transferred to the active sites of the hydrogenase to enhance H₂ production. Inspired by the success of biohybrids of enzymes and semiconducting nanoparticles, photocatalytic biohybrids of QDs and microbes have been constructed and applied to H₂ production. E. coli cells were incubated with In³⁺ and cysteine to grow In₂S₃ QDs on the bacterial surface to obtain In₂S₃@E. coli biohybrids.¹³⁰ The as-prepared biohybrids were supplemented with AgNO₃ to obtain AglnS₂/In₂S₃@E. coli via ion exchange. The electrons from photoexcited AglnS₂/In₂S₃ under illumination were transferred to closely attached E. coli cells, promoting the intracellular electron transport efficiency to enhance the production of H₂ (Fig. 7B). The E. coli cells with AglnS₂/In₂S₃ assembled on them produced substantially more H₂ compared to the E. coli cells without engineering. In this biosystem, QDs were relatively distant from the intracellular enzymes, thus electrons from the photoexcited QDs needed to be transported through the cell membrane into the cell. The biosynthesis of intracellular QDs eliminates the process of transmembrane electron transfer, enabling microbial cells to use electrons from photoexcited QDs more efficiently. Intracellular CdSe_xS_1−x QDs were biosynthesized by culturing E. coli in LB media containing Na₂SeO₃ and CdCl₂.¹³¹ The QDs drove more efficient generation of intracellular NADH, thereby enhancing the production of H₂via the formate-reducing pathway. Compared to E. coli cells with extracellular QDs, the biohybrid containing intracellular QDs achieved a H₂ production rate that was 2.6 times higher and exhibited a higher light energy conversion efficiency of 27.6%. By incubating E. coli under anaerobic conditions instead of aerobic ones, the biosynthetic efficiency of CdSe QDs was increased by two orders of magnitude, resulting in an E. coli–QD hybrid system with a quantum efficiency of 28.7% for H₂ production under visible light.⁹⁹ The as-assembled biohybrid system was applied in the treatment of wastewater containing organic chemicals to achieve reuse of waste resources and sustainable energy production.

4.2.3 Fine chemical production. In addition to the production of H₂, QD–microbe biohybrids can be used to produce fine chemicals under irradiation. A Methanosarcina barkeri–CdS biohybrid system was constructed by incubating M. barkeri with cysteine and Cd²⁺ to convert CO₂ to CH₄.¹³² Under light excitation, CdS QDs assembled on M. barkeri cells generated electrons that could be used to catalyze the reduction of ferredoxin involved in methanogenesis (Fig. 7C). Compared to wild-type M. barkeri cells, the production of CH₄ by the biohybrids was approximately 14-fold higher. Similarly, by coating CdS on the surface of Rhodopseudomonas palustris cells, the biohybrids could be applied to produce C₂₊ compounds and NH₃.¹³³ By adding Cd(NO₃)₂ and cysteine to the culture of R. palustris, CdS QDs were biosynthesized and loaded on the surface of the bacteria. The assembled biohybrid system produced 39% more solid biomass, 17% more carotenoids and 35% more poly-β-hydroxybutyrate than wild-type R. palustris.

The biological nitrogen fixation performance of microbes could also be significantly enhanced by assembling QD–microbe biohybrids¹³⁴ (Fig. 7D). It was recently reported that Azotobacter vinelandii was able to internalize supplemented QDs in the environment during growth, and the resulting biohybrids containing intracellular QDs were effective at enhancing nitrogen fixation efficiency.¹³⁵ Photoexcited QDs have the potential to enhance other biochemical reactions in microbial cells by pumping electrons to the pathways, and thus the use of QD–microbes for other new applications, such as the bioproduction of high-value chemicals, can be explored in the future.

5. Conclusion and outlook

Biosynthesis of QDs by microbes including bacteria, fungi, and viruses has been explored as a green alternative approach to chemical synthesis. Early studies primarily focused on cadmium QDs and sulfide QDs. Recently, the biosynthesis of other types of QDs has also been investigated, for example Ag₂Se QDs biosynthesized by S. cerevisiae. Owing to the surface modification by microbial peptides and proteins, QDs synthesized by microorganisms exhibit better biocompatibility and can thus be readily used in bio-related applications. By modifying the cultivation conditions of microbes or genetically engineering the microbes, the QD biosynthesis process can be regulated to modulate the size, structure, and composition of QDs.

There are still some unanswered questions and challenges to address associated with the microbial biosynthesis of QDs. The biosynthetic process is closely related to the detoxification process of metal ions. However, the influence of the biosynthesized QDs on the microbial cells has hardly been investigated.^25,114 Although the biosynthesis of QDs substantially attenuated the toxicity of metal ions, the growth and physiology of microbes were still affected.¹³⁵ In addition, other properties of microbial cells can also be affected by the biosynthesized QDs. For example, the Young's modulus of S. cerevisiae cells with intracellular biosynthetic CdSe QDs was approximately 2 MPa larger than that of wild-type cells, indicating that the nanomechanical strength was significantly improved after biosynthesis.¹³⁶ More efforts are needed to study in detail the effects of biosynthesized QDs on host microorganisms. Such information is also important for applications involving self-assembled QD–microbe biohybrids.

Previously, microbially biosynthesized QDs required time-consuming isolation and purification steps to remove microbial cells before application. QD–microbe biohybrids have been assembled by constructed microbial cells containing intracellular or extracellular biosynthesized QDs.⁹⁹ This biosystem integrates the advantages of QDs and microbes. For instance, as QDs have been used in bioimaging and photodynamic therapy,^16,137 QD–microbe hybrids can be applied in the same scenario and microbial cells can serve as the delivery vehicles. It has been demonstrated that the bacterial outer membrane vesicles secreted can target tumor cells and inhibit tumors,¹³⁸ and such vesicles can be engineered for photodynamic antitumor therapy.¹³⁹ It is envisioned that QDs can be encapsulated in the outer membrane vesicles during the bacterial QD biosynthetic process and be used as antitumor agents.

Owing to the photovoltaic properties of QDs, biological processes involving high-energy electrons can be enhanced by illumination in a QD–microbe biohybrid system. Recent studies have focused on H₂ and chemical (e.g., acetate) production by QD–microbe biohybrids. Potentially other reactions that can be enhanced by microbial electron transfer, for example polymerization, can also be facilitated by forming QD–microbe hybrids. Microbes have been used to produce structurally diverse materials including polymers.^140,141 By coupling the oxygen reduction systems of bacteria with the copper-mediated atom transfer radical polymerization process, polymers were formed in situ on the bacterial surface.¹⁴² It has been demonstrated that the extracellular electron transfer of bacteria is critical to the activity of the copper catalyst and thus contributes to the atom transfer radical polymerization.^143,144 By increasing the bacterial electron flux, a catalyst-free system was developed to synthesize polymers via radical polymerization.¹⁴⁵ QDs can absorb energy from light to produce electrons and can enhance the electron flux of microbes.^146,147 QD–microbe biohybrids can potentially enhance the performance of microbe-mediated polymerization and be used to create engineered living materials.

There are still many areas of QD biosynthesis that need to be advanced. Most of the studies on the microbial biosynthesis of QDs are based on model strains. Bacterial biosynthesis has focused on E. coli, while fungal biosynthesis has focused on S. cerevisiae. As QDs biosynthesized by acidophilic or thermophilic bacteria exhibit unique features, the biosynthetic capability of non-model microbes needs to be explored. Knowledge on the regulation of QD biosynthesis in microbes is still limited. The roles of S and Se metabolic pathways in the microbial biosynthesis of QDs have been relatively well studied. It has also been unveiled that metal efflux has an impact on QD biosynthesis. However, the effects of other biological pathways on QD biosynthesis have hardly been investigated. Moreover, the regulation of biosynthesis in non-model microbes (e.g., extremophilic microbes) also needs to be studied in the future to help optimize and tailor the QD biosynthesis by them.

Understanding the regulation also facilitates the modification of biosynthesized QDs to obtain materials with desired properties. Due to their distinct optical properties, QDs are alternative materials to organic fluorescent dyes and fluorescent proteins for biomedical applications. However, the QDs typically need to be modified to improve their biocompatibility or to target certain organelles, for example, CdSe/ZnS QDs were coupled with designed peptides to target the nucleus.¹⁴⁸ Such coupling is commonly achieved via chemical reactions. Although microbially biosynthesized QDs have proteins attached to the surface and exhibit better biocompatibility, the composition of the protein corona is not defined. Genetic engineering techniques can be applied to bind nanoparticles with desired peptides. For example, gold-binding peptides expressed by genetically engineered E. coli cells facilitated the formation of gold nanoparticles and the assembly of the cells and nanoparticles.¹⁴⁹ Likewise, genes encoding QD-binding peptides can be engineered into microbial cells to attach a designed peptide sequence to the surface of biosynthesized QDs. The binding peptide sequence segment can be fused with other functional peptides or proteins, such as fluorescent proteins and localization peptides, to endow the resulting QDs with desired functionalities.

The toxicity of QDs has been a challenge that needs to be solved for biological applications. As mentioned above, decoration of biosynthesized QDs by designed peptides in genetically engineered microbes is a potential solution to attenuate the toxicity. Alternatively, introduction of other nontoxic metals (e.g., Zn) into biosynthesized QDs containing toxic metals (e.g., CdS) can effectively reduce the toxicity. In addition, QDs with low toxicity can be obtained by coating QDs with a nontoxic shell to form a core–shell structure. Procedures to biosynthesize QDs with doping or core–shell structures have been successfully established in microbes and can be further explored in the future.

Apart from the toxicity of QDs, there are several other challenges associated with their practical applications, such as the persistence of QDs in biological systems and their improper pharmacokinetics and pharmacodynamics.¹⁵⁰ For example, QDs can cause oxidative stress in biosystems, potentially resulting in cell and tissue damage, as well as the elimination of the QDs.⁹ While surface modifications of QDs can enhance their biocompatibility and pharmacological profiles, complex physiological conditions can alter such modifications, potentially compromising the therapeutic efficacy and targeting functionality of QDs or promoting the aggregation of QDs into larger particles that may persist in the organism.^151,152 Combining QDs with microbes may offer a potential means to address these limitations. In a study conducted by Ding et al., a genetically engineered probiotic E. coli was combined with black phosphorus QDs through electrostatic adsorption, and the resulting complexes were applied in photodynamic therapy.¹⁵³ The biohybrids improved the targeting capability of QDs and alleviated their cellular immune responses. The utilization of genetically engineered probiotic bacteria to synthesize QDs and form biohybrids holds promise as a strategy for biomedical applications.

One of the primary hurdles in the microbial synthesis of QDs is associated with their production at an industrial scale. Due to the current limited understanding of the mechanisms involved in the biosynthesis of QDs, the quality of biosynthesized QDs is compromised particularly when scaling up the synthesis process. Additionally, the toxicity of substrates, such as heavy metals, negatively affects cellular viability in industrial production, resulting in lower yields of QDs. Hence, it is crucial to conduct more comprehensive research on the process and regulation of the microbial synthesis of QDs. The development of genetically engineered microbes with enhanced substrate tolerance and improved control of QD biosynthesis is also necessary.

When the above challenges and issues are addressed and more knowledge about the regulation of QD biosynthesis is accumulated, it is expected that microbially biosynthesized QDs will find more diverse and innovative applications in different scientific and technological fields. Recent advancements in synthetic biology will accelerate this process and enable the biosynthesis of QDs with more diverse and customized properties and functions.

Author contributions

Conceptualization, Y. Z. and Y. W.; data curation, C. J. and W. X.; project administration, J. L. and X. Z.; supervision, J. L.; validation, W. X.; writing – original draft, C. J. and W. X.; writing – review & editing, K. J., L. Y., H. L., Z. L., X. Z., Y. W., and Y. Z.

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

We acknowledge the financial support from the Shanghai Sailing Program (20YF1413900), the National Natural Science Foundation of China (32000036), and the Innovative Research Team of High-Level Local Universities in Shanghai.

References

1. P.-C. Lin, S. Lin, P. C. Wang and R. Sridhar, Techniques for physicochemical characterization of nanomaterials, Biotechnol. Adv., 2014, 32, 711–726.
2. L. A. Kolahalam, I. V. K. Viswanath, B. S. Diwakar, B. Govindh, V. Reddy and Y. L. N. Murthy, Review on nanomaterials: Synthesis and applications, Mater. Today: Proc., 2019, 18, 2182–2190.
3. M. M. Modena, B. Rühle, T. P. Burg and S. Wuttke, Nanoparticle Characterization: What to Measure?, Adv. Mater., 2019, 31, e1901556.
4. X. M. Gong, D. L. Huang, Y. G. Liu, Z. W. Peng, G. M. Zeng, P. Xu, M. Cheng, R. Z. Wang and J. Wan, Remediation of contaminated soils by biotechnology with nanomaterials: bio-behavior, applications, and perspectives, Crit. Rev. Biotechnol., 2018, 38, 455–468.
5. W. W. Tang, G. M. Zeng, J. L. Gong, J. Liang, P. Xu, C. Zhang and B. B. Huang, Impact of humic/fulvic acid on the removal of heavy metals from aqueous solutions using nanomaterials: a review, Sci. Total Environ., 2014, 468–469, 1014–1027.
6. M. Ahmadi, H. Elmongy, T. Madrakian and M. Abdel-Rehim, Nanomaterials as sorbents for sample preparation in bioanalysis: A review, Anal. Chim. Acta, 2017, 958, 1–21.
7. L. J. Zhang, L. Xia, H. Y. Xie, Z. L. Zhang and D. W. Pang, Quantum Dot Based Biotracking and Biodetection, Anal. Chem., 2019, 91, 532–547.
8. W. C. Chan, D. J. Maxwell, X. Gao, R. E. Bailey, M. Han and S. Nie, Luminescent quantum dots for multiplexed biological detection and imaging, Curr. Opin. Biotechnol., 2002, 13, 40–46.
9. V. G. Reshma and P. V. Mohanan, Quantum dots: Applications and safety consequences, J. Lumin., 2019, 205, 287–298.
10. Q. Xu, J. J. Gao, S. Y. Wang, Y. Wang, D. Liu and J. C. Wang, Quantum dots in cell imaging and their safety issues, J. Mater. Chem. B, 2021, 9, 5765–5779.
11. B. Liu, B. Jiang, Z. P. Zheng and T. C. Liu, Semiconductor quantum dots in tumor research, J. Lumin., 2019, 209, 61–68.
12. A. M. Wagner, J. M. Knipe, G. Orive and N. A. Peppas, Quantum dots in biomedical applications, Acta Biomater., 2019, 94, 44–63.
13. S. J. Rosenthal, J. C. Chang, O. Kovtun, J. R. McBride and I. D. Tomlinson, Biocompatible quantum dots for biological applications, Chem. Biol., 2011, 18, 10–24.
14. N. Öcal, A. Ceylan and F. Duman, Intracellular biosynthesis of PbS quantum dots using Pseudomonas aeruginosa ATCC 27853: evaluation of antibacterial effects and DNA cleavage activities, World J. Microbiol. Biotechnol., 2020, 36, 147–156.
15. Y. Honda, Y. Shinohara, M. Watanabe, T. Ishihara and H. Fujii, Photo-biohydrogen Production by Photosensitization with Biologically Precipitated Cadmium Sulfide in Hydrogen-Forming Recombinant Escherichia coli, ChemBioChem, 2020, 21, 3389–3397.
16. H. F. Bao, Z. S. Lu, X. Q. Cui, Y. Qiao, J. Guo, J. M. Anderson and C. M. Li, Extracellular microbial synthesis of biocompatible CdTe quantum dots, Acta Biomater., 2010, 6, 3534–3541.
17. F. P. García de Arquer, D. V. Talapin, V. I. Klimov, Y. Arakawa, M. Bayer and E. H. Sargent, Semiconductor quantum dots: Technological progress and future challenges, Science, 2021, 373, eaaz8541.
18. K. Kalyanasundaram, E. Borgarello, D. Duonghong and M. Grätzel, Cleavage of water by visible-light irradiation of colloidal CdS solutions; inhibition of photocorrosion by RuO₂, Angew. Chem., Int. Ed. Engl., 1981, 20, 987–988.
19. A. Valizadeh, H. Mikaeili, M. Samiei, S. M. Farkhani, N. Zarghami, M. Kouhi, A. Akbarzadeh and S. Davaran, Quantum dots: synthesis, bioapplications, and toxicity, Nanoscale Res. Lett., 2012, 7, 480–493.
20. S. Wei, R. Zhang, Y. Liu, H. Ding and Y. L. Zhang, Graphene quantum dots prepared from chemical exfoliation of multiwall carbon nanotubes: An efficient photocatalyst promoter, Catal. Commun., 2016, 74, 104–109.
21. X. Y. Cao, C. P. Ding, C. L. Zhang, W. Gu, Y. H. Yan, X. H. Shi and Y. Z. Xian, Transition metal dichalcogenide quantum dots: synthesis, photoluminescence and biological applications, J. Mater. Chem. B, 2018, 6, 8011–8036.
22. D. Thomas, H. O. Lee, K. C. Santiago, M. Pelzer, A. Kuti, E. Jenrette and M. Bahoura, Rapid Microwave Synthesis of Tunable Cadmium Selenide (CdSe) Quantum Dots for Optoelectronic Applications, J. Nanomater., 2020, 1–8,  DOI:10.1155/2020/5056875.
23. A. B. Bourlinos, A. Stassinopoulos, D. Anglos, R. Zboril, M. Karakassides and E. P. Giannelis, Surface functionalized carbogenic quantum dots, Small, 2008, 4, 455–458.
24. H. Nishimura, Y. X. Lin, M. Hizume, T. Taniguchi, N. Shigekawa, T. Takagi, S. Sobue, S. Kawai, E. Okuno and D. Kim, Hydrothermal synthesis of ZnSe:Mn quantum dots and their optical properties, AIP Adv., 2019, 9, 025223.
25. L. Hu, C. Zhang, G. M. Zeng, G. Q. Chen, J. Wan, Z. Guo, H. P. Wu, Z. G. Yu, Y. Y. Zhou and J. F. Liu, Metal-based quantum dots: synthesis, surface modification, transport and fate in aquatic environments and toxicity to microorganisms, RSC Adv., 2016, 6, 78595–78610.
26. I. Hussain, N. B. Singh, A. Singh, H. Singh and S. C. Singh, Green synthesis of nanoparticles and its potential application, Biotechnol. Lett., 2016, 38, 545–560.
27. S. Azizi, M. B. Ahmad, F. Namvar and R. Mohamad, Green biosynthesis and characterization of zinc oxide nanoparticles using brown marine macroalga Sargassum muticum aqueous extract, Mater. Lett., 2014, 116, 275–277.
28. Y. Yang, G. I. N. Waterhouse, Y. L. Chen, D. Sun-Waterhouse and D. P. Li, Microbial-enabled green biosynthesis of nanomaterials: Current status and future prospects, Biotechnol. Adv., 2022, 55, 107914.
29. S. R. Stuerzenbaum, M. Hoeckner, A. Panneerselvam, J. Levitt, J.-S. Bouillard, S. Taniguchi, L.-A. Dailey, R. A. Khanbeigi, E. V. Rosca, M. Thanou, K. Suhling, A. V. Zayats and M. Green, Biosynthesis of luminescent quantum dots in an earthworm, Nat. Nanotechnol., 2013, 8, 57–60.
30. M. N. Borovaya, A. P. Naumenko, N. A. Matvieieva, Y. B. Blume and A. I. Yemets, Biosynthesis of luminescent CdS quantum dots using plant hairy root culture, Nanoscale Res. Lett., 2014, 9, 686–692.
31. C. T. Dameron, R. N. Reese, R. K. Mehra, A. R. Kortan, P. J. Carroll, M. L. Steigerwald, L. E. Brus and D. R. Winge, Biosynthesis of cadmium sulphide quantum semiconductor crystallites, Nature, 1989, 338, 596–597.
32. Z. Y. Yan, C. X. Yao, D. Y. Wan, L. L. Wang, Q. Q. Du, Z. Q. Li and S. M. Wu, A sensitive and simple method for detecting Cu²⁺ in plasma using fluorescent Bacillus amyloliquefaciens, containing intracellularly biosynthesized CdSe quantum dots, Enzyme Microb. Technol., 2018, 119, 37–44.
33. S. A. Kumar, A. A. Ansary, A. Ahmad and M. I. Khan, Extracellular Biosynthesis of CdSe Quantum Dots by the Fungus, Fusarium Oxysporum, J. Biomed. Nanotechnol., 2007, 3, 190–194.
34. J. Liu, D. Zheng, L. Zhong, A. Gong, S. Wu and Z. Xie, Biosynthesis of biocompatibility Ag₂Se quantum dots in Saccharomyces cerevisiae and its application, Biochem. Biophys. Res. Commun., 2021, 544, 60–64.
35. Z. W. Zhang, J. Chen, Q. L. Yang, K. Lan, Z. Y. Yan and J. Q. Chen, Eco-friendly intracellular microalgae synthesis of fluorescent CdSe QDs as a sensitive nanoprobe for determination of imatinib, Sens. Actuators, B, 2018, 263, 625–633.
36. W. Shenton, T. Douglas, M. Young, G. Stubbs and S. Mann, Inorganic-Organic Nanotube Composites from Template Mineralization of Tobacco Mosaic Virus, Adv. Mater., 1999, 11, 253–256.
37. Z. Yang, L. Lu, V. F. Berard, Q. He, C. J. Kiely, B. W. Berger and S. McIntosh, Biomanufacturing of CdS quantum dots, Green Chem., 2015, 17, 3775–3782.
38. Y. Y. Feng, K. E. Marusak, L. C. You and S. Zauscher, Biosynthetic transition metal chalcogenide semiconductor nanoparticles: Progress in synthesis, property control and applications, Curr. Opin. Colloid Interface Sci., 2018, 38, 190–203.
39. X. Q. Li, H. Z. Xu, Z. S. Chen and G. F. Chen, Biosynthesis of Nanoparticles by Microorganisms and Their Applications, J. Nanomater., 2011, 1–16,  DOI:10.1155/2011/270974.
40. R. Y. Sweeney, C. Mao, X. Gao, J. L. Burt, A. M. Belcher, G. Georgiou and B. L. Iverson, Bacterial biosynthesis of cadmium sulfide nanocrystals, Chem. Biol., 2004, 11, 1553–1559.
41. M. Eisenstein, Bacteria Find Work as Amateur Chemists, Nat. Methods, 2005, 2, 6–7.
42. Q. Y. Yuan, M. Bomma and Z. G. Xiao, Enhanced Silver Nanoparticle Synthesis by Escherichia Coli Transformed with Candida Albicans Metallothionein Gene, Materials, 2019, 12, 4180.
43. S. H. Kang, K. N. Bozhilov, N. V. Myung, A. Mulchandani and W. Chen, Microbial synthesis of CdS nanocrystals in genetically engineered E. coli, Angew. Chem., Int. Ed., 2008, 47, 5186–5189.
44. T. J. Park, S. Y. Lee, N. S. Heo and T. S. Seo, In vivo synthesis of diverse metal nanoparticles by recombinant Escherichia coli, Angew. Chem., Int. Ed., 2010, 49, 7019–7024.
45. Y. Choi, T. J. Park, D. C. Lee and S. Y. Lee, Recombinant Escherichia coli as a biofactory for various single- and multi-element nanomaterials, Proc. Natl. Acad. Sci. U. S. A., 2018, 115, 5944–5949.
46. C. C. Mi, Y. Y. Wang, J. P. Zhang, H. Q. Huang, L. R. Xu, S. Wang, X. X. Fang, J. Fang, C. B. Mao and S. K. Xu, Biosynthesis and characterization of CdS quantum dots in genetically engineered Escherichia coli, J. Biotechnol., 2011, 153, 125–132.
47. A. Y. Chen, Z. Deng, A. N. Billings, U. O. Seker, M. Y. Lu, R. J. Citorik, B. Zakeri and T. K. Lu, Synthesis and patterning of tunable multiscale materials with engineered cells, Nat. Mater., 2014, 13, 515–523.
48. P. Chellamuthu, F. Tran, K. P. T. Silva, M. S. Chavez, M. Y. El-Naggar and J. Q. Boedicker, Engineering bacteria for biogenic synthesis of chalcogenide nanomaterials, Microb. Biotechnol., 2019, 12, 161–172.
49. A. K. Suresh, M. J. Doktycz, W. Wang, J. W. Moon, B. Gu, H. M. Meyer, D. K. Hensley, D. P. Allison, T. J. Phelps and D. A. Pelletier, Monodispersed biocompatible silver sulfide nanoparticles: facile extracellular biosynthesis using the gamma-proteobacterium, Shewanella oneidensis, Acta Biomater., 2011, 7, 4253–4258.
50. S. Qi, M. Zhang, X. Guo, L. Yue, J. Wang, Z. Shao and B. Xin, Controlled extracellular biosynthesis of ZnS quantum dots by sulphate reduction bacteria in the presence of hydroxypropyl starch as a mediator, J. Nanopart. Res., 2017, 19, 212.
51. S. Shirodkar, S. Reed, M. Romine and D. Saffarini, The octahaem SirA catalyses dissimilatory sulfite reduction in Shewanella oneidensis MR-1, Environ. Microbiol., 2011, 13, 108–115.
52. X. Xiao, X. Han, L. G. Wang, F. Long, X. L. Ma, C. C. Xu, X. B. Ma, C. X. Wang and Z. Y. Liu, Anaerobically photoreductive degradation by CdS nanocrystal: Biofabrication process and bioelectron-driven reaction coupled with Shewanella oneidensis MR-1, Biochem. Eng. J., 2020, 154, 107466.
53. X. Xiao, X.-B. Ma, H. Yuan, P.-C. Liu, Y.-B. Lei, H. Xu, D.-L. Du, J.-F. Sun and Y.-J. Feng, Photocatalytic properties of zinc sulfide nanocrystals biofabricated by metal-reducing bacterium Shewanella oneidensis MR-1, J. Hazard. Mater., 2015, 288, 134–139.
54. X. Xiao, Q. Y. Liu, X. R. Lu, T. T. Li, X. L. Feng, Q. Li, Z. Y. Liu and Y. J. Feng, Self-assembly of complex hollow CuS nano/micro shell by an electrochemically active bacterium Shewanella oneidensis MR-1, Int. Biodeterior. Biodegrad., 2017, 116, 10–16.
55. N.-Q. Zhou, L.-J. Tian, Y.-C. Wang, D.-B. Li, P.-P. Li, X. Zhang and H.-Q. Yu, Extracellular biosynthesis of copper sulfide nanoparticles by Shewanella oneidensis MR-1 as a photothermal agent, Enzyme Microb. Technol., 2016, 95, 230–235.
56. V. G. Debabov, T. A. Voeikova, A. S. Shebanova, K. V. Shaitan, L. M. Novikova and M. P. Kirpichnikov, Bacterial synthesis of silver sulfide nanoparticles, Nanotechnol. Russ., 2013, 8, 269–276.
57. L.-X. Xu, Y.-Z. Wang, D. Zhou, M.-Y. Chen, X.-J. Yang, X.-M. Ye and Y.-C. Yong, Bio-Metabolism-Driven Crystalline-Engineering of CdS Quantum Dots for Highly Active Photocatalytic H₂ Evolution, ChemistrySelect, 2021, 6, 3702–3706.
58. P. Dhandapani, S. Maruthamuthu and G. Rajagopal, Bio-mediated synthesis of TiO₂ nanoparticles and its photocatalytic effect on aquatic biofilm, J. Photochem. Photobiol., B, 2012, 110, 43–49.
59. J. B. Rivest and P. K. Jain, Cation exchange on the nanoscale: an emerging technique for new material synthesis, device fabrication, and chemical sensing, Chem. Soc. Rev., 2013, 42, 89–96.
60. B. J. Beberwyck, Y. Surendranath and A. P. Alivisatos, Cation Exchange: A Versatile Tool for Nanomaterials Synthesis, J. Phys. Chem. C, 2013, 117, 19759–19770.
61. N. Órdenes-Aenishanslins, G. Anziani-Ostuni, J. P. Monrás, A. Tello, D. Bravo, D. Toro-Ascuy, R. Soto-Rifo, P. N. Prasad and J. M. Pérez-Donoso, Bacterial Synthesis of Ternary CdSAg Quantum Dots through Cation Exchange: Tuning the Composition and Properties of Biological Nanoparticles for Bioimaging and Photovoltaic Applications, Microorganisms, 2020, 8, 631–649.
62. C. Gallardo, J. P. Monrás, D. O. Plaza, B. Collao, L. A. Saona, V. Durán-Toro, F. A. Venegas, C. Soto, G. Ulloa, C. C. Vásquez, D. Bravo and J. M. Pérez-Donoso, Low-temperature biosynthesis of fluorescent semiconductor nanoparticles (CdS) by oxidative stress resistant Antarctic bacteria, J. Biotechnol., 2014, 187, 108–115.
63. A. Syed and A. Ahmad, Extracellular biosynthesis of platinum nanoparticles using the fungus Fusarium oxysporum, Colloids Surf., B, 2012, 97, 27–31.
64. F. Alani, M. Moo-Young and W. Anderson, Biosynthesis of silver nanoparticles by a new strain of Streptomyces sp. compared with Aspergillus fumigatus, World J. Microbiol. Biotechnol., 2012, 28, 1081–1086.
65. A. Yadav, K. Kon, G. Kratosova, N. Duran, A. P. Ingle and M. Rai, Fungi as an efficient mycosystem for the synthesis of metal nanoparticles: progress and key aspects of research, Biotechnol. Lett., 2015, 37, 2099–2120.
66. P. Mohanpuria, N. K. Rana and S. K. Yadav, Biosynthesis of nanoparticles: technological concepts and future applications, J. Nanopart. Res., 2008, 10, 507–517.
67. M. Kowshik, W. Vogel, J. Urban, S. K. Kulkarni and K. M. Paknikar, Microbial Synthesis of Semiconductor PbS Nanocrystallites, Adv. Mater., 2002, 14, 815.
68. J. G. S. Mala and C. Rose, Facile production of ZnS quantum dot nanoparticles by Saccharomyces cerevisiae MTCC 2918, J. Biotechnol., 2014, 170, 73–78.
69. R. Cui, H. H. Liu, H. Y. Xie, Z. L. Zhang, Y. R. Yang, D. W. Pang, Z. X. Xie, B. B. Chen, B. Hu and P. Shen, Living Yeast Cells as a Controllable Biosynthesizer for Fluorescent Quantum Dots, Adv. Funct. Mater., 2009, 19, 2359–2364.
70. G. V. Smirnova and O. N. Oktyabrsky, Glutathione in Bacteria, Biochemistry, 2005, 70, 1199–1211.
71. S. S. Gill, N. A. Anjum, M. Hasanuzzaman, R. Gill, D. K. Trivedi, I. Ahmad, E. Pereira and N. Tuteja, Glutathione and glutathione reductase: a boon in disguise for plant abiotic stress defense operations, Plant Physiol. Biochem., 2013, 70, 204–212.
72. Y.-P. Gu, R. Cui, Z.-L. Zhang, Z.-X. Xie and D.-W. Pang, Ultrasmall near-infrared Ag₂Se quantum dots with tunable fluorescence for in vivo imaging, J. Am. Chem. Soc., 2012, 134, 79–82.
73. R. Cui, Y.-P. Gu, Z.-L. Zhang, Z.-X. Xie, Z.-Q. Tian and D.-W. Pang, Controllable synthesis of PbSe nanocubes in aqueous phase using a quasi-biosystem, J. Mater. Chem., 2012, 22, 3713.
74. Y. Li, R. Cui, P. Zhang, B.-B. Chen, Z.-Q. Tian, L. Li, B. Hu, D.-W. Pang and Z.-X. Xie, Mechanism-Oriented Controllability of Intracellular Quantum Dots Formation: The Role of Glutathione Metabolic Pathway, ACS Nano, 2013, 7, 2240–2248.
75. M. Shao, R. Zhang, C. Wang, B. Hu, D. W. Pang and Z. X. Xie, Living cell synthesis of CdSe quantum dots: Manipulation based on the transformation mechanism of intracellular Se-precursors, Nano Res., 2018, 11, 2498–2511.
76. E. Priyadarshini, S. S. Priyadarshini, B. G. Cousins and N. Pradhan, Metal-Fungus interaction: Review on cellular processes underlying heavy metal detoxification and synthesis of metal nanoparticles, Chemosphere, 2021, 274, 129976.
77. T. Yamaguchi, Y. Tsuruda, T. Furukawa, L. Negishi, Y. Imura, S. Sakuda, E. Yoshimura and M. Suzuki, Synthesis of CdSe Quantum Dots Using Fusarium oxysporum, Materials, 2016, 9, 855.
78. Y. G. Yin, X. Y. Yang, L. G. Hu, Z. Q. Tan, L. X. Zhao, Z. F. Zhang, J. Liu and G. B. Jiang, Superoxide-Mediated Extracellular Biosynthesis of Silver Nanoparticles by the Fungus Fusarium oxysporum, Environ. Sci. Technol. Lett., 2016, 3, 160–165.
79. P. Kaur, P. Jain, A. Kumar and R. Thakur, Biogenesis of PbS Nanocrystals by Using Rhizosphere Fungus i.e., Aspergillus sp. Isolated from the Rhizosphere of Chickpea, BioNanoScience, 2014, 4, 189–194.
80. A. Syed, M. H. A. Saedi, A. H. Bahkali, A. M. Elgorgan, M. Kharat, K. Pai, J. Pichtel and A. Ahmad, αAu₂S nanoparticles: Fungal-mediated synthesis, structural characterization and bioassay, Green Chem. Lett. Rev., 2021, 15, 61–70.
81. S. Y. Lee, J. S. Lim and M. T. Harris, Synthesis and application of virus-based hybrid nanomaterials, Biotechnol. Bioeng., 2012, 109, 16–30.
82. C. Mao, C. E. Flynn, A. Hayhurst, R. Sweeney, J. F. Qi, G. Georgiou, B. Iverson and A. M. Belcher, Viral assembly of oriented quantum dot nanowires, Proc. Natl. Acad. Sci. U. S. A., 2003, 100, 6946–6951.
83. J. M. Lee, J. W. Choi, I. Jeon, Y. Zhu, T. Yang, H. Chun, J. Shin, J. Park, J. Bang, K. Lim, W. G. Kim, Y. Kim, H. Jeong, E. J. Choi, V. Devaraj, J. S. Nam, H. Ahn, Y. C. Kang, B. Han, M. Song, J. W. Oh and C. Mao, High quantum efficiency and stability of biohybrid quantum dots nanojunctions in bacteriophage-constructed perovskite, Mater. Today Nano, 2021, 13, 100099.
84. Y.-H. Cui, L.-L. Li, L.-J. Tian, N.-Q. Zhou, D.-F. Liu, P. K. S. Lam and H.-Q. Yu, Synthesis of CdS_1-xSe_x quantum dots in a protozoa Tetrahymena pyriformis, Appl. Microbiol. Biotechnol., 2019, 103, 973–980.
85. L. H. Xiong, J. W. Tu, Y. N. Zhang, L. L. Yang, R. Cui, Z. L. Zhang and D. W. Pang, Designer cell-self-implemented labeling of microvesicles in situ with the intracellular-synthesized quantum dots, Sci. China: Chem., 2020, 63, 448–453.
86. H. Trabelsi, I. Azzouz, S. Ferchichi, O. Tebourbi, M. Sakly and H. Abdelmelek, Nanotoxicological evaluation of oxidative responses in rat nephrocytes induced by cadmium, Int. J. Nanomed., 2013, 8, 3447–3453.
87. M. Cheraghizade, F. Jamali-Sheini, R. Yousefi, F. Niknia, M. R. Mahmoudian and M. Sookhakian, The effect of tin sulfide quantum dots size on photocatalytic and photovoltaic performance, Mater. Chem. Phys., 2017, 195, 187–194.
88. M. Alizadeh-Ghodsi, M. Pourhassan-Moghaddam, A. Zavari-Nematabad, B. Walker, N. Annabi and A. Akbarzadeh, State-of-the-Art and Trends in Synthesis, Properties, and Application of Quantum Dots-Based Nanomaterials, Part. Part. Syst. Charact., 2019, 36, 1800302.
89. S. M. Wu, Y. L. Su, R. R. Liang, X. X. Ai, J. Qian, C. Wang, Q. Jchen and Z. Y. Yan, Crucial factors in biosynthesis of fluorescent CdSe quantum dots in Saccharomyces cerevisiae, RSC Adv., 2015, 5, 79184–79191.
90. Z.-Y. Yan, Q.-Q. Du, J. Qian, D.-Y. Wan and S.-M. Wu, Eco-friendly intracellular biosynthesis of CdS quantum dots without changing Escherichia coli's antibiotic resistance, Enzyme Microb. Technol., 2017, 96, 96–102.
91. S. Y. Qi, Y. H. Miao, J. Chen, H. C. Chu, B. Y. Tian, B. R. Wu, Y. J. Li and B. P. Xin, Controlled Biosynthesis of ZnCdS Quantum Dots with Visible-Light-Driven Photocatalytic Hydrogen Production Activity, Nanomaterials, 2021, 11, 1357.
92. S. Y. Qi, J. Chen, X. W. Bai, Y. H. Miao, S. H. Yang, C. Qian, B. R. Wu, Y. J. Li and B. P. Xin, Quick extracellular biosynthesis of low-cadmium ZnxCd_1-xS quantum dots with full-visible-region tuneable high fluorescence and its application potential assessment in cell imaging, RSC Adv., 2021, 11, 21813–21823.
93. X. Q. Li, D. E. Yin, S. Z. Kang, J. Mu, J. Wang and G. D. Li, Preparation of cadmium-zinc sulfide nanoparticles modified titanate nanotubes with high visible-light photocatalytic activity, Colloids Surf., A, 2011, 384, 749–751.
94. M. Yang, Y. B. Wang, Y. K. Ren, E. Z. Liu, J. Fan and X. Y. Hu, Zn/Cd ratio-dependent synthetic conditions in ternary ZnCdS quantum dots, J. Alloys Compd., 2018, 752, 260–266.
95. O. Y. Wang, L. Wang, Z. H. Li, Q. L. Xu, Q. L. Lin, H. Z. Wang, Z. L. Du, H. B. Shen and L. S. Li, High-efficiency, deep blue ZnCdS/Cd_xZn_1-xS/ZnS quantum-dot-light-emitting devices with an EQE exceeding 18%, Nanoscale, 2018, 10, 5650–5657.
96. M. Ashengroph, A. Khaledi and E. M. Bolbanabad, Extracellular biosynthesis of cadmium sulphide quantum dot using cell-free extract of Pseudomonas chlororaphis CHR05 and its antibacterial activity, Process Biochem., 2020, 89, 63–70.
97. G. Ulloa, B. Collao, M. Araneda, B. Escobar, S. Álvarez, D. Bravo and J. M. Pérez-Donoso, Use of acidophilic bacteria of the genus Acidithiobacillus to biosynthesize CdS fluorescent nanoparticles (quantum dots) with high tolerance to acidic pH, Enzyme Microb. Technol., 2016, 95, 217–224.
98. A. M. Mohs, H. Duan, B. A. Kairdolf, A. M. Smith and S. Nie, Proton-resistant quantum dots: Stability in gastrointestinal fluids and implications for oral delivery of nanoparticle agents, Nano Res., 2009, 2, 500–508.
99. X. M. Wang, L. Chen, R. L. He, S. Cui, J. Li, X. Z. Fu, Q. Z. Wu, H. Q. Liu, T. Y. Huang and W. W. Li, Anaerobic self-assembly of a regenerable bacteria-quantum dot hybrid for solar hydrogen production, Nanoscale, 2022, 14, 8409–8417.
100. S. Ghosh, R. Ahmad, K. Banerjee, M. F. AlAjmi and S. Rahman, Mechanistic Aspects of Microbe-Mediated Nanoparticle Synthesis, Front. Microbiol., 2021, 12, 638068.
101. J. Zhou, Y. Yang and C. Y. Zhang, Toward Biocompatible Semiconductor Quantum Dots: From Biosynthesis and Bioconjugation to Biomedical Application, Chem. Rev., 2015, 115, 11669–11717.
102. A. Barik, D. Biswal, A. Arun and V. Balasubramanian, Biodetoxification of Heavy Metals Using Biofilm Bacteria, Environ. Agric. Microbiol., 2021, 39–61.
103. W. Q. Yang, X. H. Li, L. L. Fei, W. Z. Liu, X. L. Liu, H. Y. Xu and Y. C. Liu, A review on sustainable synthetic approaches toward photoluminescent quantum dots, Green Chem., 2022, 24, 675–700.
104. P. Prabhakaran, M. A. Ashraf and W. S. Aqma, Microbial stress response to heavy metals in the environment, RSC Adv., 2016, 6, 109862–109877.
105. C. Cobbett and P. Goldsbrough, Phytochelatins and metallothioneins: roles in heavy metal detoxification and homeostasis, Annu. Rev. Plant Biol., 2002, 53, 159–182.
106. F. Ramezani, M. Ramezani and S. Talebi, Mechanistic aspects of biosynthesis of nanoparticles by several microbes, Nanocon, 2010, 10, 12–14.
107. J. P. Monrás, V. Díaz, D. Bravo, R. A. Montes, T. G. Chasteen, I. O. Osorio-Román, C. C. Vásquez and J. M. Pérez-Donoso, Enhanced Glutathione Content Allows the In Vivo Synthesis of Fluorescent CdTe Nanoparticles by Escherichia coli, PLoS One, 2012, 7, e48657.
108. Y. T. Wang, H. Chen, Z. X. Huang, M. Yang, H. L. Yu, M. C. Peng, Z. Y. Yang and S. D. Chen, Structural characterization of cystathionine gamma-lyase smCSE enables aqueous metal quantum dot biosynthesis, Int. J. Biol. Macromol., 2021, 174, 42–51.
109. A. G. Cordente, A. Heinrich, I. S. Pretorius and J. H. Swiegers, Isolation of sulfite reductase variants of a commercial wine yeast with significantly reduced hydrogen sulfide production, FEMS Yeast Res., 2009, 9, 446–459.
110. G. L. Sun, E. E. Reynolds and A. M. Belcher, Using yeast to sustainably remediate and extract heavy metals from waste waters, Nat. Sustainability, 2020, 3, 303–311.
111. C. Rensing, B. Mitra and B. P. Rosen, The zntA gene of Escherichia coli encodes a Zn(II)-translocating P-type ATPase, Proc. Natl. Acad. Sci. U. S. A., 1997, 94, 14326–14331.
112. M. R. Binet and R. K. Poole, Cd(II), Pb(II) and Zn(II) ions regulate expression of the metal-transporting P-type ATPase ZntA in Escherichia coli, FEBS Lett., 2000, 473, 67–70.
113. T.-T. Zhu, L.-J. Tian, S.-S. Yu and H.-Q. Yu, Roles of cation efflux pump in biomineralization of cadmium into quantum dots in Escherichia coli, J. Hazard. Mater., 2021, 412, 125248.
114. B. Gidwani, V. Sahu, S. S. Shukla, R. Pandey, V. Joshi, V. K. Jain and A. Vyas, Quantum dots: Prospectives, toxicity, advances and applications, J. Drug Delivery Sci. Technol., 2021, 61, 102308.
115. A. S. Karakoti, R. Shukla, R. Shanker and S. Singh, Surface functionalization of quantum dots for biological applications, Adv. Colloid Interface Sci., 2015, 215, 28–45.
116. R. Bilan, F. Fleury, I. Nabiev and A. Sukhanova, Quantum dot surface chemistry and functionalization for cell targeting and imaging, Bioconjugate Chem., 2015, 26, 609–624.
117. C. Y. Zhang and L. W. Johnson, Microfluidic control of fluorescence resonance energy transfer: breaking the FRET limit, Angew. Chem., Int. Ed., 2007, 46, 3482–3485.
118. F. Ma, C. C. Li and C. Y. Zhang, Development of quantum dot-based biosensors: principles and applications, J. Mater. Chem. B, 2018, 6, 6173–6190.
119. F. Ma, Q. Zhang and C. Y. Zhang, Catalytic Self-Assembly of Quantum-Dot-Based MicroRNA Nanosensor Directed by Toehold-Mediated Strand Displacement Cascade, Nano Lett., 2019, 19, 6370–6376.
120. Z. Y. Wang, D. L. Li, X. Tian and C. Y. Zhang, A copper-free and enzyme-free click chemistry-mediated single quantum dot nanosensor for accurate detection of microRNAs in cancer cells and tissues, Chem. Sci., 2021, 12, 10426–10435.
121. Y. Zhang, J. Xiao, Y. Zhu, L. Tian, W. Wang, T. Zhu, W. Li and H. Yu, Fluorescence Sensor Based on Biosynthetic CdSe/CdS Quantum Dots and Liposome Carrier Signal Amplification for Mercury Detection, Anal. Chem., 2020, 92, 3990–3997.
122. P. Uddandarao, R. M. Balakrishnan, A. Ashok, S. Swarup and P. Sinha, Bioinspired ZnS:Gd Nanoparticles Synthesized from an Endophytic Fungi Aspergillus flavus for Fluorescence-Based Metal Detection, Biomimetics, 2019, 4, 11.
123. J. Ge, Q. Jia, W. Liu, L. Guo, Q. Liu, M. Lan, H. Zhang, X. Meng and P. Wang, Red-Emissive Carbon Dots for Fluorescent, Photoacoustic, and Thermal Theranostics in Living Mice, Adv. Mater., 2015, 27, 4169–4177.
124. A. M. Smith, M. C. Mancini and S. Nie, Bioimaging: second window for in vivo imaging, Nat. Nanotechnol., 2009, 4, 710–711.
125. L. C. Spangler, L. Lu, C. J. Kiely, B. W. Berger and S. McIntosh, Biomineralization of PbS and PbS–CdS core–shell nanocrystals and their application in quantum dot sensitized solar cells, J. Mater. Chem. A, 2016, 4, 6107–6115.
126. W. X. Wang, Y. H. Liu, T. H. Shi, J. L. Sun, F. Y. Mo and X. Q. Liu, Biosynthesized Quantum Dot for Facile and Ultrasensitive Electrochemical and Electrochemiluminescence Immunoassay, Anal. Chem., 2020, 92, 1598–1604.
127. X.-B. Li, C.-H. Tung and L.-Z. Wu, Semiconducting quantum dots for artificial photosynthesis, Nat. Rev. Chem., 2018, 2, 160–173.
128. Y. C. Yuan, N. Jin, P. Saghy, L. Dube, H. Zhu and O. Chen, Quantum Dot Photocatalysts for Organic Transformations, J. Phys. Chem. Lett., 2021, 12, 7180–7193.
129. C. A. Caputo, L. Wang, R. Beranek and E. Reisner, Carbon nitride-TiO₂ hybrid modified with hydrogenase for visible light driven hydrogen production, Chem. Sci., 2015, 6, 5690–5694.
130. Z. Jiang, B. Wang, J. C. Yu, J. Wang, T. An, H. Zhao, H. Li, S. Yuan and P. K. Wong, AglnS₂/In₂S₃ heterostructure sensitization of Escherichia coli for sustainable hydrogen production, Nano Energy, 2018, 46, 234–240.
131. S. Cui, L.-J. Tian, J. Li, X.-M. Wang, H.-Q. Liu, X.-Z. Fu, R.-L. He, P. K. S. Lam, T.-Y. Huang and W.-W. Li, Light-assisted fermentative hydrogen production in an intimately-coupled inorganic-bio hybrid with self-assembled nanoparticles, Chem. Eng. J., 2022, 428, 131254.
132. J. Ye, J. Yu, Y. Y. Zhang, M. Chen, X. Liu, S. G. Zhou and Z. He, Light-driven carbon dioxide reduction to methane by Methanosarcina barkeri-CdS biohybrid, Appl. Catal., B, 2019, 257, 117916.
133. B. Wang, Z. F. Jiang, J. C. Yu, J. F. Wang and P. K. Wong, Enhanced CO₂ reduction and valuable C₂₊ chemical production by a CdS-photosynthetic hybrid system, Nanoscale, 2019, 11, 9296–9301.
134. B. Wang, K. M. Xiao, Z. F. Jiang, J. F. Wang, J. C. Yu and P. K. Wong, Biohybrid photoheterotrophic metabolism for significant enhancement of biological nitrogen fixation in pure microbial cultures, Energy Environ. Sci., 2019, 12, 2185–2191.
135. S. Koh, Y. Choi, I. Lee, G. M. Kim, J. Kim, Y. S. Park, S. Y. Lee and D. C. Lee, Light-Driven Ammonia Production by Azotobacter vinelandii Cultured in Medium Containing Colloidal Quantum Dots, J. Am. Chem. Soc., 2022, 144, 10798–10808.
136. Q.-Y. Luo, Y. Lin, Y. Li, L.-H. Xiong, R. Cui, Z.-X. Xie and D.-W. Pang, Nanomechanical analysis of yeast cells in CdSe quantum dot biosynthesis, Small, 2014, 10, 699–704.
137. V. Biju, S. Mundayoor, R. V. Omkumar, A. Anas and M. Ishikawa, Bioconjugated quantum dots for cancer research: present status, prospects and remaining issues, Biotechnol. Adv., 2010, 28, 199–213.
138. O. Y. Kim, H. T. Park, N. T. H. Dinh, S. J. Choi, J. Lee, J. H. Kim, S. W. Lee and Y. S. Gho, Bacterial outer membrane vesicles suppress tumor by interferon-gamma-mediated antitumor response, Nat. Commun., 2017, 8, 626.
139. W. R. Zhuang, Y. F. Wang, Y. Lei, L. P. Zuo, A. Q. Jiang, G. H. Wu, W. D. Nie, L. L. Huang and H. Y. Xie, Phytochemical Engineered Bacterial Outer Membrane Vesicles for Photodynamic Effects Promoted Immunotherapy, Nano Lett., 2022, 22, 4491–4500.
140. P. Q. Nguyen, N. D. Courchesne, A. Duraj-Thatte, P. Praveschotinunt and N. S. Joshi, Engineered Living Materials: Prospects and Challenges for Using Biological Systems to Direct the Assembly of Smart Materials, Adv. Mater., 2018, 30, 1704847.
141. C. Gilbert and T. Ellis, Biological Engineered Living Materials: Growing Functional Materials with Genetically Programmable Properties, ACS Synth. Biol., 2019, 8, 1–15.
142. E. P. Magennis, F. Fernandez-Trillo, C. Sui, S. G. Spain, D. J. Bradshaw, D. Churchley, G. Mantovani, K. Winzer and C. Alexander, Bacteria-instructed synthesis of polymers for self-selective microbial binding and labelling, Nat. Mater., 2014, 13, 748–755.
143. G. Fan, C. M. Dundas, A. J. Graham, N. A. Lynd and B. K. Keitz, Shewanella oneidensis as a living electrode for controlled radical polymerization, Proc. Natl. Acad. Sci. U. S. A., 2018, 115, 4559–4564.
144. G. Fan, A. J. Graham, J. Kolli, N. A. Lynd and B. K. Keitz, Aerobic radical polymerization mediated by microbial metabolism, Nat. Chem., 2020, 12, 638–646.
145. M. D. Nothling, H. Cao, T. G. McKenzie, D. M. Hocking, R. A. Strugnell and G. G. Qiao, Bacterial Redox Potential Powers Controlled Radical Polymerization, J. Am. Chem. Soc., 2021, 143, 286–293.
146. A. M. Smith and S. Nie, Semiconductor Nanocrystals: Structure, Properties, and Band Gap Engineering, Acc. Chem. Res., 2010, 43, 190–200.
147. J. A. Caputo, L. C. Frenette, N. Zhao, K. L. Sowers, T. D. Krauss and D. J. Weix, General and Efficient C-C Bond Forming Photoredox Catalysis with Semiconductor Quantum Dots, J. Am. Chem. Soc., 2017, 139, 4250–4253.
148. C.-W. Kuo, D.-Y. Chueh, N. Singh, F.-C. Chien and P. Chen, Targeted nuclear delivery using peptide-coated quantum dots, Bioconjugate Chem., 2011, 22, 1073–1080.
149. H. Dong, D. A. Sarkes, J. J. Rice, M. M. Hurley, A. J. Fu and D. N. Stratis-cullum, Living Bacteria-Nanoparticle Hybrids Mediated through Surface-Displayed Peptides, Langmuir, 2018, 34, 5837–5848.
150. Z. Chen, H. Chen, H. Meng, G. Xing, X. Gao, B. Sun, X. Shi, H. Yuan, C. Zhang, R. Liu, F. Zhao, Y. Zhao and X. Fang, Bio-distribution and metabolic paths of silica coated CdSeS quantum dots, Toxicol. Appl. Pharmacol., 2008, 230, 364–371.
151. Y. Zhang, Y. Zhang, G. Hong, W. He, K. Zhou, K. Yang, F. Li, G. Chen, Z. Liu, H. Dai and Q. Wang, Biodistribution, pharmacokinetics and toxicology of Ag₂S near-infrared quantum dots in mice, Biomaterials, 2013, 34, 3639–3646.
152. Y. Su, F. Peng, Z. Jiang, Y. Zhong, Y. Lu, X. Jiang, Q. Huang, C. Fan, S. T. Lee and Y. He, In vivo distribution, pharmacokinetics, and toxicity of aqueous synthesized cadmium-containing quantum dots, Biomaterials, 2011, 32, 5855–5862.
153. S. Ding, Z. Liu, C. Huang, N. Zeng, W. Jiang and Q. Li, Novel Engineered Bacterium/Black Phosphorus Quantum Dot Hybrid System for Hypoxic Tumor Targeting and Efficient Photodynamic Therapy, ACS Appl. Mater. Interfaces, 2021, 13, 10564–10573.

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