Xi-Le
Hu†
a,
Ying
Shang†
a,
Kai-Cheng
Yan†
b,
Adam C.
Sedgwick
c,
Hui-Qi
Gan
a,
Guo-Rong
Chen
a,
Xiao-Peng
He
*a,
Tony D.
James
*be and
Daijie
Chen
*d
aKey Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, School of Chemistry and Molecular Engineering, Frontiers Center for Materiobiology and Dynamic Chemistry, East China University of Science and Technology, 130 Meilong Rd, Shanghai 200237, China. E-mail: xphe@ecust.edu.cn
bDepartment of Chemistry, University of Bath, Claverton Down, Bath, BA2 7AY, UK. E-mail: t.d.james@bath.ac.uk
cDepartment of Chemistry, The University of Texas at Austin, Austin, Texas 78712-1224, USA
dSchool of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan RD, Shanghai 200240, China. E-mail: cdj@sjtu.edu.cn
eSchool of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang 453007, China
First published on 24th February 2021
The excessive use of antibiotics has led to a rise in drug-resistant bacteria. These “superbugs” are continuously emerging and becoming increasingly harder to treat. As a result, new and effective treatment protocols that have minimal risks of generating drug-resistant bacteria are urgently required. Advanced nanomaterials are particularly promising due to their drug loading/releasing capabilities combined with their potential photodynamic/photothermal therapeutic properties. In this review, 0-dimensional, 1-dimensional, 2-dimensional, and 3-dimensional nanomaterial-based systems are comprehensively discussed for bacterial-based diagnostic and treatment applications. Since the use of these platforms as antibacterials is relatively new, this review will provide appropriate insight into their construction and applications. As such, we hope this review will inspire researchers to explore antibacterial-based nanomaterials with the aim of developing systems for clinical applications.
In the area of materials sciences, graphene and various other carbon-based nanomaterials have emerged as excellent components for conductor and battery-based applications.17–19 The significance of these findings has inspired the design of new and improved nanomaterials and the identification of valuable optical and thermal properties.20,21 These important characteristics have attracted considerable interest from biomedical researchers who wish to repurpose these nanomaterials for diagnostic and therapeutic applications.22–25 Nanomaterials have now been tailored towards a range of biology-based applications, including use as drug delivery systems (DDSs) in order to enhance the selectivity and efficacies of specific therapeutics.26–29 In addition, nanomaterials have exhibited the ability to perform photodynamic/photothermal therapy (upon light irradiation, PDT uses photosensitizers to convert environmental oxygen to reactive oxygen species (ROS), and PTT converts photoenergy to heat upon light activation, respectively) for disease treatment.30 Moreover, nanomaterials co-loaded with therapeutic agents have been shown to provide synergistic effects with PDT/PTT, which reduces the required therapeutic dose and minimalizes off-target toxicities,31 while theranostics (combined therapeutic and diagnostic) has been developed where imaging agents have been loaded onto nanomaterials to facilitate the ability to “sense and treat”.
Nanomaterials are defined as materials with at least one length dimension being less than 100 nm.32 Recently, several reviews summarizing the development of nanomaterials for antibacterial applications have been reported. Niu and co-workers reviewed the antibacterial properties of different metals and metal oxides including titanium derivatives, zinc oxide, nickel, copper and copper oxide, gold, palladium, selenium and iron.33 In another review, Truong and co-workers summarized the antibacterial mechanisms of different metallic nanomaterials.34 One of the most common mechanisms involves physical interaction with the bacterial surface, which kills bacteria through membrane damage. Which, results in ion release that causes enzyme inhibition or nucleic acid degradation, and ROS production. The authors concluded that there is an emerging trend for developing stimulus-activated nanomaterials, which require an external triggering element for the materials to function, affording “activatable” antibacterial materials. The most extensively used triggering elements include light (PDT/PTT) and magnetic force. Focusing on a variety of mechanisms facilitating antibacterial function, Song and co-workers prepared a comprehensive review on polymeric, antibiotic-free materials.35 The diverse antibacterial mechanisms include suppression of bacterial metabolism, catalytic bacterial killing by nanozymes and drug-loading/releasing. Moreover, the real-world applications of the as-developed strategies were deliberated for wound dressings, medical implants and food packaging. However, to the best of our knowledge, a summary of antibacterial nanomaterials in terms of their dimensionality has not been published (Scheme 1).
Scheme 1 Schematic illustration of the low-dimensional materials, including their antibacterial mechanisms, covered in this review. |
Dimensionality is an important asset of nanomaterials, which can change the intrinsic properties of the materials. Low dimensional materials including 0-D (zero-dimensional), 1-D (one-dimensional), 2-D (two-dimensional) and 3-D (three-dimensional) nanomaterials have attracted the interest of materials physicists and chemists owing to their exceptional mechanical, magnetic, electric and optical properties. Significantly, differences in dimensionality could lead to different biological activities for the low-dimensional materials. The low-dimensional materials and their antibacterial mechanisms covered in this review are described in Table 1.
Composition of nanomaterials | Antibacterial mechanism | Ref. | |
---|---|---|---|
0-D nanomaterials | |||
AgNP-based nanomaterials | Nanocrystalline cellulose (NCC)-coated AgNPs (AgNPs/NCC) | AgNP-triggered oxidative stress, protein dysfunction, and membrane and DNA damages | 48 |
D-Cysteine-functionalised AgNPs (D-Cys-AgNPs) | D-Cysteine inhibits biofilm formation, thus enhancing the therapeutic effect of AgNPs | 50 | |
Dextrin-based nanocomposite hydrogels (Dex-G5-Ag) | Controlled release of AgNPs, inducing oxidative stress, protein dysfunction, and membrane and DNA damages | 57 | |
Template-guided synthesis of ultrafine Ag NPs of around 2 nm using water-soluble and biocompatible γ-cyclodextrin metal–organic frameworks (CD-MOFs) | Ag+ ion release leading to protein dysfunction, and membrane and DNA damages | 54 | |
Integrating silver nanoparticles in situ into hydrogel materials (AgNP-hydrogel) | Kinetically-controlled release of antibacterial silver ions | 60 | |
Nanomaterials based on other metallic and carbon-based particles | Mesoporous silica-supported Ag-bismuth (Bi) (Ag-Bi@SiO2) | Ag-Bi@SiO2 significantly increased local temperature due to light absorption of BiNPs, leading to disruption of cell integrity and acceleration of silver ion release | 51 |
CeO2-decorated nanoparticle MOFs (MOF@CeO2NPs) | Inhibition of the function of extracellular ATP by CeO2 nanoparticles, leading to disruption of initial bacterial adhesion. In addition, planktonic bacteria are killed by cytotoxic reactive oxygen species (ROS) generated by the MOFs | 70 | |
Carbon nanodots (CNDs) (CND-250) | Programmed cell death of bacteria induced by carbon dots (C-dots) with different surface charges | 71 | |
Nanomaterials based on polymeric particles | Poly(ionic liquid)/PVA hydrogel | Electrostatic interaction between phosphate groups in the cell membrane of bacteria and the positive charges of the poly(ionic liquid) enhanced the cell membrane permeability, causing leakage of cytoplasmic contents. | 58 |
Dual-mode antibacterial conjugated polymer nanoparticles (DMCPNs) | Dual PTT/PDT effect killing drug-resistant bacteria | 78 | |
Organic nanoparticles based on polymers that have a hydrophobic skeleton and hydrophilic side chain modified with protonated primary amines (PDCP) | Binding with bacterial LPS (lipopolysaccharides) to disrupt membrane integrity | 79 | |
Porphyrin-based porous organic polymer, FePPOPBFPB | Catalytic transformation of H2O2 to ˙OH species for bacterial eradication | 80 | |
1-D nanomaterials | |||
Nanowires | Silver nanowires (AgNWs) | Silver ion release by dissolution of the material after the oxidation of metallic silver | 86 |
Co-V mixed metal oxide (MMO) nanowires (Co3V2O8) | Peroxidase-mediated transformation of low concentrations of H2O2 to toxic ROS species | 96 | |
Nanofibers | Cu2+-based coordination polymer nanofibers (CuO/MnO2 core nanostructures) | ROS generation and release of Cu2+ ions | 89 |
Nanorods | PEG-functionalised AuNRs (PU-Au-PEG) | Inhibition of bacterial adhesion and PTT for multidrug-resistant bacteria | 91 |
Bi2S3-coated AuNRs (Au@Bi2S3) | Dual-mode PTT/PDT | 92 | |
γ-AlOOH, γ-MnOOH, and α-Mn2O3 nanorods | Firm bacterial adhesion causing cell wrapping and morphological disruption | 94 | |
Nanotubes | AgNO3 mixed with N,N-bis(pyridyl-4-methyl)-N-fluorenyl-9-methoxycarbonyl (Fmoc)-L-glutamate (4MPFG) leading to gelation (4MPFG) | Disruption of membrane integrity inducing DNA condensation | 87 |
Nanoribbon-based supra-structure | Polycationic porphyrin (Pp4N) mixed with GNR-PEO2000 (Pp4N/GNR) | Dual-mode PDT/PTT | 103 |
2-D nanomaterials | |||
Graphene-based nanomaterials | GO and reduced GO (rGO) | GO destructs bacteria by cell membrane damage through chemical reactions, whereas rGO induces mechanical stress and pierces the cell membrane | 109 |
Loading of sodium 1-naphthalenesulfonate (NA) onto reduced GO for chelation of AgNPs, producing AgNP-NA-rGO (AgNP-NA-rGO) | Cytoplasmic membrane damage facilitating reaction between silver ions and cytoplasmic constituents | 116 | |
PEG-functionalised GO mixed with AgNPs (GO-PEG-Ag) | Bacterial structure damage and production of ROS, causing cytoplasm leakage and metabolic disorder | 117 | |
Loading of GO with AgNPs and CoFe2O4NPs (Ag-CoFe2O4-GO) | Membrane damage | 118 | |
GO nanocomposites assembled with QASs (quaternary ammonium salts) | Physical disruption of bacterial membrane | 112 | |
2-D MoS2-based nanomaterials | Chitosan-coated 2-D MoS2 (CS@MoS2) | Membrane damage, and oxidation of intracellular proteins and lipids | 136 |
AgBrNPs mixed with MoS2 nanosheets AgBr@MoS2 | PDT | 128 | |
Quaternized chitosan (QCS)-modified MoS2 nanoflakes (QCS-MoS2) | Membrane adhesion followed by photothermal antibiotic release | 123 | |
α-CD-modified 2-D MoS2 nanosheets assembled with a heat sensitive NO donor, N,N′-di-sec-butyl-N,N′-dinitroso-1,4-phenylenediamine (BNN6) | Photothermal acceleration of glutathione oxidation, disrupting the balance of antioxidants, and thus DNA damage of bacteria | 124 and 125 | |
Nanomaterials based on GO@MoS2 hybrids | PEG-2-D MoS2/rGO nanoflakes loaded with streptomycin sulfate (PEG-MoS2/rGO-SS) | PTT-based physical damage of bacteria, interruption of protein synthesis and production of oxidative stress | 137 |
GO-MoS2 nanocomposite film (GO-MoS2) | ROS-dependent oxidative stress | 119 | |
Nanomaterials based on other graphene-like materials | Ti3C2Tx MXene nanosheets | Damage of cell membrane causing the release of cytoplasmic materials. ROS-dependent and -independent stress induction | 129 |
2-D lamellar membranes consisting of restacked WS2 nanosheets | Retards bacterial growth by deformation of bacterial cell, and damage of the cell wall | 132 | |
Black phosphorus (BP)/AuNP nanocomposite (BP/AuNP) | Concerted PTT, “nanoknife” effect, and production of oxidative stress | 138 | |
3-D nanomaterials | |||
Metal–organic frameworks | MOF@COF nanozyme | Tight capture of bacteria followed by in situ ROS generation | 143 |
Mesoporous bioactive glass (MBG) loaded with in situ grown silver (Ag@pMBG) | Silver ion release via molecular diffusion and degradation, leading to single-electron reduction of O2 interrupting the respiratory chain of bacteria | 145 | |
Ag2S nanoparticle- decorated nanocubes (Ag2S/NCs) | Dual-mode PTT/PDT | 146 | |
Mg–Al double-layered rGO (Mg-Al@rGO) | Protein degradation and GSH loss through the induction of oxidative stress | 153 | |
AgNP-deposited carbon aerogels (p-BC/AgNP) | Silver ion release leading to protein dysfunction and DNA damage | 156 | |
Defect-rich adhesive molybdenum disulfide MoS2/rGO vertical heterostructure (VHS MoS2/rGO) | Effective bacteria capture through local topological interactions, followed by ROS-based destruction of bacteria | 154 | |
Other 3-D nanomaterials | TiO2 nanorod arrays | Dual-mode PTT/PDT | 147 |
Covalent-organic frameworks | Degradable 3D-printed polylactic acid (PLA) scaffold | Mitochondrial damage, leading to apoptosis | 155 |
The dimensional difference of the materials causes their antimicrobial mechanisms to differ. For example, 0-D nanomaterials can serve as both a metal ion-releasing therapeutic agent and carrier for antibiotic delivery. Due to their small size, 0-D nanoparticles can also be incorporated into hydrogels or loaded onto flat materials for practical applications.36 A representative clinical application is the use of a silver-nanoparticle-based hydrogel for treatment of bacterial infection on the skin.33,34 1-D nanomaterials are upgraded in respect to surface area and are free from the drawbacks of internal deposition compared to 0-D, while they share properties with both 0-D and their 2-D counterparts. 1-D rod-like nanomaterials are similar to 0-D with respect to performance and applications, while 1-D ribbon-like nanomaterials are more similar to 2-D because they are mostly derived from graphene.37 2-D nanomaterials owing to their large surface area have been used for the loading of antibiotics and other therapeutic agents and combined with PDT/PTT. They can also be used for the direct eradication of bacteria by physical cutting as assisted by their sharp edge.37 2-D materials are also degradable in human bodies thus avoiding the toxicity brought about by 0-D or 1-D nanomaterials.38 3-D nanomaterials are more likely to be a combination of 0-D, 1-D, or 2-D components, so they could exhibit the combined properties of 0-D, 1-D and 2-D nanomaterials resulting in composite systems with improved antibacterial properties.39 With the continuing development of materials science, the biocompatibilities of different nanomaterials have been greatly improved, which will stimulate the development of enhanced properties for improved clinical applicability. Within this review, to allow ease of understanding, we have separated antibacterial nanomaterials according to their dimensionality. In our review, we will discuss stimulus-activated and target-responsive low-dimensional nanomaterials that have been recently developed for antibacterial applications, with particular emphasis on the parameters that determine their practical applicability including the antibacterial spectrum, biocompatibility for clinical use and selectivity towards other pathogens.
Fig. 1 Schematic illustration of Ag-Bi@SiO2 NPs that release Ag+ ions and provide PTT for the treatment of bacteria in vitro and in vivo. Image reprinted with permission from ref. 51. Copyright 2020, Wiley-VCH. |
Hydrogels are attractive for effective wound management, due to their excellent biocompatibility and therapeutic loading ability, including the incorporation of nanoparticles.55–58 More specifically, stimulus-responsive/smart hydrogels are particularly attractive for a range of biomedical applications;59 however, long term stability issues are often observed. To overcome this, Zhao and co-workers demonstrated that the simple loading of AgNPs into colour-responsive hydrogels prevented bacterial adhesion, hydrogel damage, and maintained the colour-responsive properties during application and long term storage.60 More recently, Dai and co-workers reported on the design of an acid-responsive hydrogel, Dex-G5-Ag, for the controlled release of AgNPs for the treatment of bacterial infection.57 Dex-G5-Ag hydrogels were formed by Schiff-base condensation between dextran (Dex-CHO) and an amino-functionalized dendrimer, G5-Ag (AgNPs encapsulated). The as-formed hydrogel was shown to degrade in an acidic environment and release AgNPs (Fig. 2). This strategy exhibited minimal cytotoxicity towards normal cell lines and proved effective for the treatment of a variety of bacteria including E. coli, P. aeruginosa, S. aureus, and S. epidermidis, and the effects were further evaluated using mouse-infection models. Other examples include the use of poly(ionic liquid)/poly(vinyl alcohol) (PVA) hydrogels for the development of antibacterial wound dressings.58
Fig. 2 Schematic illustration of the construction of an AgNP loaded hydrogel, Dex-G5-Ag, which displays potent antibacterial activity. Image reprinted with permission from ref. 57. Copyright 2018, American Chemical Society. |
However, silver as a first-generation antibacterial material exhibits clear toxicity towards tissues, since it can be deposited in bodies leading to heavy-metal accumulation, which makes it hard for the approach to be clinically-accepted. Effective as it is, it could also kill other cells due to low selectivity. Functionalization or encapsulation of sliver could to some extent solve the problem but this approach is still far from satisfactory. Over the last several years, researchers have explored and evaluated the ability of non-silver-based nanomaterials for the treatment of bacteria. Firstly, other metals were evaluated, which mainly included a similar but much milder metal: gold. Gold nanoparticles (AuNPs) are well-established multifunctional 0-D nanomaterials used for biosensing, as drug carriers, as well as for theranostic, PDT/PTT and immunology applications.61–66 Perry and co-workers reported a unique antibacterial AuNP-strategy, in which gold ions (AuCl4−) were reduced and capped by cefaclor a second-generation antibiotic (Fig. 3).65 AuNP-cefaclor was shown to have potent antibacterial activity towards S. aureus and E. coli, while the individual use of AuNPs and cefaclor had minimal therapeutic effects (Fig. 3). Similarly, Jiang and co-workers explored AuNPs modified with 4,6-diamino-2-pyrimidinethiol (DAPT) as antibacterial agents (DGNPs).67,68 More recently, various particle sizes of DGNPs were evaluated against bacteria in order to correlate particle size with antibacterial activity.67 The antibacterial effects were assessed against Gram-negative and Gram-positive bacteria. Ultrasmall DGNPs < 2 nm (uDGNPs) displayed broad spectrum activity and as a result they were incorporated into agarose gels for wound dressing applications. The same authors evaluated a range of N-heterocyclic molecules with AuNPs, which displayed broad spectrum activity. Optimised antibacterial activities were achieved by varying the molar ratios of N-heterocycles with the precursor of AuNPs, HAuCl4.69 Compared to silver, gold-based agents are particularly delicate towards tissues, but this is also accompanied with a weakened antibacterial effect. Consequently, effective gold-based approaches are always assisted by using co-loaded antibiotics or other agents in order to attain acceptable performance.
Fig. 3 (a) Schematic illustration of the synthesis of a AuNP-cefaclor complexed system for developing novel antimicrobial coatings. (b and c) Histogram plots showing antibacterial activity of the different systems on S. aureus (b) and E. coli (c) after different incubation times. Images reprinted with permission from ref. 65. Copyright 2010, The Royal Society of Chemistry. |
Apart from the issues discussed above regarding AgNPs and AuNPs, these 0-D nanomaterials are expensive and result in metal ion release into the environment. These limitations prevent their scale-up and widespread use for clinical applications. Consequently, other metals are also being evaluated. Recently, Qu and co-workers developed CeO2-decorated nanoparticle MOFs (MOF@CeO2NPs) as dual modal therapeutics for the treatment of planktonic bacteria and bacterial biofilms.70 Adenosine triphosphate (ATP) is an essential small molecule for all living organisms. More specifically, ATP plays a crucial role in bacterial adhesion and biofilm formation. Exploiting the known binding affinity of the lanthanide cerium (Ce) for ATP, CeO2 prevented biofilm formation through ATP extraction. Subsequent 638 nm light irradiation of the MOF@CeO2 NPs facilitated the production of cytotoxic ROS to kill planktonic bacteria. The ROS generation was facilitated through a MOF consisting of zirconium (Zr) clusters and a PDT agent, tetracarboxyl phenylporphyrin. Overall, combination therapy using the MOF@CeO2NPs was shown to be an effective treatment for bacteria and biofilm inhibition.
In order to further remove the toxicity of metals, other inorganic material systems were developed. A representative example was demonstrated by Yang and co-workers, in which carbon nanodots (CNDs) were designed to simultaneously treat and image bacteria.71 These antibacterial CNDs were developed using the wide-spectrum antibiotic metronidazole72 as the sole carbon source. CNDs-250 were prepared at 250 °C for 3 h and 8 h, respectively (Fig. 4a). Evaluation of the optical density (OD) of bacterial solutions demonstrated a 71.7% inhibition of P. gingivalis at low concentrations (1.25 μg mL−1), similar to that of metronidazole (Fig. 4b). In contrast, when using control systems or treating other bacteria (Fig. 4c–e), the inhibition effects disappeared, thus demonstrating a selective effect towards P. gingivalis only. Based on this observation, the effects of CNDs-250 were further screened against a variety of bacteria, and it was found that CNDs-250 displayed significant activity towards obligate anaerobes (P. micros, P. intermedia, P. gingvivalis and Fusobacterium) rather than facultative anaerobes (S. mutans), obligate aerobes, or microaerophilic (E. coli) bacteria, which is similar to metronidazole which is the carbon source of the CNDs-250. The low toxicity towards human cell lines combined with their fluorescence properties enabled their use in cell labelling and imaging experiments. Importantly, CNDs were shown to be selective for bacteria in comparison to metronidazole only, displaying 60% cell viability in MC3T3-E1 cells. This underscores the significance of nanomaterials for antibacterial applications. MC3T3-E1 cells incubated with CNDs-250 displayed clear fluorescence emission when excited using green, blue, and UV light excitation, respectively. Another example reported by Qu and co-workers,73 evaluated the programmed cell death of bacteria induced by carbon dots (C-dots) with different surface charges. This report provides unique insights into the design of C-dots for antibacterial applications.
Fig. 4 (a) Schematic illustration of CNDs-3h and CNDs-8h prepared from metronidazole and differing by reaction time. (b and c) Growth curves of P. gingivalis after incubation with various concentrations of metronidazole and CNDs-250 (b), and CA-CDs (c) for 24 h. (d and e) Growth curves of S. mutans (d) and E. coli (e) after incubation with various concentrations of CNDs-250 for 24 h. Images reprinted with permission from ref. 71. Copyright 2017, The Royal Society of Chemistry. |
Yang and co-workers found that GQDs derived from graphene oxide (GO-GQDs) displayed weak antibacterial activity. This was believed to be due to their zero Gaussian curvature. In their study, they rationalised that the preparation of GQDs from C60 would provide a non-zero Gaussian curvature and provide improved antibacterial activity. These C60-GQDs exhibited significant antibacterial activity against S. aureus only (Fig. 5a),74 which was believed to be a result of the disruption of the bacterial cell envelope (confirmed by TEM images). Interestingly, E. coli was shown to have smooth surfaces regardless of the type of GQDs used (Fig. 5b). Scanning electron microscopy (SEM) images indicated that C60-GQD-treated S. aureus cells were coated with NPs, whereas, GO-GQD-treated S. aureus cells and all E. coli cells (no matter which type of GQDs was used to treat them) remained smooth (Fig. 5c). This selectivity for S. aureus demonstrated the importance of both the nanomaterial source and shape for physical contact-mediated treatment of bacterial species (i.e. S. aureus).
Fig. 5 (a) Bacterial assays using C60-GQDs and GO-GQDs towards both Gram-positive and Gram-negative bacteria. (b and c) TEM (b) and SEM (c) images showing the surfaces of S. aureus and E. coli cells treated with C60-GQDs and with GO-GQDs along with control groups. Image reprinted with permission from ref. 74. Copyright 2015, American Chemical Society. |
However, since all metallic and non-metallic elements are inevitably incompatible with tissues and can to some extent stay inside bodies for a long time, people have started to explore the use of polymers. Polymeric nanoparticles provide a low cost, highly degradable, and biocompatible alternative. Moreover, the homogeneity of polymeric nanoparticles is much better than metal nanoparticles, thus ensuring the stability of the antibacterial activity. A recent example was reported by Qin and co-workers,75 in which guanidine-based nanogels were developed that displayed antibacterial and antiadhesion properties. Significant antibacterial activity was observed against S. aureus and E. coli, which was successfully demonstrated using an infected mouse model. In addition, these nanogels were applied to the design of antimicrobial materials. A similar polymeric nanoparticle strategy was reported, which employed the antimicrobial functionality of N-halamine. This system possessed strong antibacterial activity towards both S. aureus and E. coli and proved stable during long term storage.76 Zhao and co-workers reported biodegradable cationic ε-poly-L-lysine/poly(ε-caprolactone) polymeric nanoparticles as new antibacterial agents towards B. subtilis, S. aureus, and E. coli.77 A photothermal agent poly(diketopyrrolopyrrole-thienothiophene) (PDP/PTT) and photosensitizer poly[2-methoxy-5-((2-ethylhexyl)oxy)-p-phenylenevinylene] (MEH-PPV) were dispersed in aqueous solution to form dual-mode conjugated nanoparticles, which displayed combined PDT and PTT effect upon activation by white light and 808 nm NIR light, respectively.78 The system was suitable for treatment of E. coli and exhibited no tissue toxicity. Very recently, new insights into polymeric nanoparticles have emerged. These include the synthesis of a monomer with two 1,2 3-triazoles and primary amines to improve water solubility and afford antibacterial activity,79 and a novel porphyrin-based porous organic polymer nanozyme prepared by the reaction of pyrrole and 4-{2,2-bis[(4-formylphenoxy)methyl]-3-(4-formylphenoxy)propoxy}benzaldehyde (BFPB) that exhibited peroxidase-like activity toward a peroxidase substrate 3,3′,5,5′-tetramethylbenzidine (TMB) with H2O2 under 808 nm NIR irradiation.80 While Cheng and co-workers in 2021 developed a polymer–antibiotic conjugate consisting of penicillin, 2-chloroethyl methacrylate (CEMA), and hydroxyethyl methacrylate (HEMA) crosslinked together and self-assembled into particles, as a strategy to develop resin-based restorative dental materials for sustained antibacterial therapy.81S. mutans biofilms resulting in dental caries were cultured and eradicated using the as-developed polymers, the slow antibiotic release discouraging bacterial resistance and ensuring long-term efficacy in the prevention of dental caries. Upon exposure to an enzymatic challenge resembling true intra-oral conditions, the efficiency of the antibacterial agent was maintained, demonstrating the potential for long-term effects and effective clinical behaviour.
With the aim of enhancing biocompatibility towards tissues, copper (Cu)-based and Au-based 1-D nanomaterials were proposed. Copper (Cu)-based 1-D nanomaterials include Cu/C, CuO nanorods and nanoplatelets, which have exhibited comparable antibacterial efficacies to known antibiotics with enhanced biocompatibility.88 More recently, Rauf and co-workers reported Cu2+-based coordination polymer nanofibers,89 that were formed from [Cu(H2O)3]2+ and HBTC (1,3,5-benzenetricarboxylic acid) (Fig. 6a). The nanofibers exhibited excellent antibacterial effects against both E. coli and S. aureus (Fig. 6b). The proposed antibacterial mechanism was the generation of ROS combined with the release of Cu2+ ions. As with AuNPs, gold nanorods (AuNRs) have been shown to exhibit a range of diagnostic and therapeutic applications.90 A recent study by Zhao and co-workers demonstrated PEG-functionalised AuNRs for the PTT treatment of multidrug-resistant S. aureus and P. aeruginosa biofilms.91 These functionalised AuNRs were used with infected mouse models in vivo. Similarly, Bi2S3-coated AuNRs (Au@Bi2S3) have been reported by Wang et al. for the light-based treatment of bacteria.92 The NIR light irradiation (808 nm) of Au@Bi2S3 resulted in the PDT/PTT-based treatment of E. coli and S. aureus (Fig. 7a), with clear inhibition seen in bacterial cultures (Fig. 7b). Interestingly, the individual use of each component resulted in minimal antibacterial activity being observed. As such, each component was required to have a good therapeutic effect.
Fig. 6 (a) Basic schematic of the growth of the [Cu(HBTC)(H2O)3]-based nanofibers. (b) Images of E. coli and S. aureus treated with different concentrations of [Cu(HBTC)(H2O)3]-based nanofibers. Images reprinted with permission from ref. 89. Copyright 2019, The Royal Society of Chemistry. |
Fig. 7 (a) Construction of Bi2S3-coated AuGNRs for the PDT/PTT-based treatment of bacteria. (b) Images of E. coli and S. aureus colonies on nutrition cultures after treatment with Au@Bi2S3 with and without laser irradiation. Images reprinted with permission from ref. 92. Copyright 2020, Elsevier B.V. |
In the area of 1-D research, oxides of metals have been investigated. For example Mn3O4-based nanorods and nanotubes have been developed by Chen et al., through a bi-directional-bi-dimensional growth model with biocompatibility comparable to gold systems.93 The antibacterial properties were confirmed using a range of bacteria including B. subtilis, S. aureus, S. faecalis, P. aeruginosa, and E. cloacae. The research further illustrated the importance of the morphology of nanomaterials, since Mn3O4 nanotubes were found to have a greater bacterial inhibition towards Gram-negative bacteria, than Mn3O4 nanorods. With a growing interest in 1-D nanomaterials as bacterial-resistant materials and for antibacterial applications, Selim and co-workers developed synthetic methods for the preparation of γ-AlOOH, γ-MnOOH, and α-Mn2O3 nanorods exhibiting biocompatibility/stability comparable to those of Mn3O4 nanorods.94 The antibacterial activity was evaluated against P. aeruginosa, S. aureus, E. coli, B. subtilis, B. pertussis, and C. albicans, and all three nanorods exhibited significant antibiofilm activity, and α-Mn2O3 was particularly effective against B. subtilis, P. aeruginosa, and B. pertussis biofilms. In particular the authors highlighted the importance of controlling the shape and the surface area of nanomaterials for achieving appropriate antibacterial efficacy. It is important to note, that many researchers have endeavoured to improve the antibacterial efficacy of 1-D nanomaterials through functionalisation with antibacterial peptides.95 Wang and co-workers reported Co-V mixed metal oxide (MMO) nanowires, which consisted of Co3V2O8 dispersed amongst Co3O4.96 Exploiting the intrinsic oxidase-like and peroxidase-like catalytic activities of Co-V MMO nanowires, in combination with low concentrations of H2O2 (50 μM), resulted in the successful treatment of E. coli. The antibacterial activity was attributed to the peroxidase-mediated transformation of H2O2 to the more harmful superoxide O2˙−. These materials offer an alternative to expensive Ag- and Au-based nanomaterials; however the homogeneity of suspension requires additional improvement. Importantly, the ability to use low concentrations of H2O2 minimises healthy tissue damage.
To solve the chronic problems caused by metals, 1-D researchers have developed systems from inorganic materials. The incorporation of non-metal/metal components into 1-D nanomaterials results in improved properties for sensing and therapeutic applications (e.g. electrochemical, fluorescence and PTT).97 Within this realm, graphene-derived 1-D nanomaterials have shown promise for antibacterial applications with not only PTT or agent-loading functions but also, a physical-cutting mechanism to assist therapy.98,99 For example, Davis and co-workers reported the combination of single-walled nanotubes (SWNTs) and lysozyme (displaying inherent antibacterial activity for Gram-positive bacteria) for the construction of multicomponent fibers.83 The cationic surfactant, tetradecyltrimethylammonium bromide was used to improve the stability of dispersions and enhance mechanical properties. CNTs are particularly attractive due to their tuneable thermal and electrical characteristics and high surface area to volume ratio. Additionally, CNTs have been shown as effective carriers for metallic NPs as well as increasing their aqueous stability and therapeutic properties. Hidal and co-workers reported the coating of multi-walled carbon nanotubes (MWCNTs) with AgNPs to develop an effective tool to prevent membrane fouling. In their study, the incorporation of AgNP-CNTs into polyethersulfone (PES) ultrafiltration (UF) membranes was efficient for antifouling applications with significant inhibitory activity towards both E. coli and S. Aureus being observed.100 With the AgNPs co-loaded into CNTs, the inherent toxicity was also avoided and the selectivity was improved. Hao et al. reported MWCNT–glucosamine–AgNP nanocomposites for the construction of functional materials with long-term antibacterial activity. Using this strategy, MWCNTs were grafted with glucosamine, which facilitated the coordination of AgNPs (Fig. 8a–d).101 This approach permitted the slow and controlled release of AgNPs, which provided long-term antibacterial activity against S. aureus over 35 days (Fig. 8e) with minimal side effects.
Fig. 8 (a) Basic schematic for the development of glucosamine-grafted CNTs and subsequent AgNP coordination. (b–d) TEM images of the CNTs (b), CNTs with glucosamine (c), and CNTs with glucosamine and AgNPs (d). (e) S. aureus survival rates in Luria–Bertani medium with treatments of MWCNT–AgNPs (control), glucosamine–AgNPs (control), and MWCNT–glucosamine–AgNPs during a 35 day period. Images reprinted with permission from ref. 101. Copyright 2017, The Royal Society of Chemistry and the Centre National de la Recherche Scientifique. |
When compared with antibacterial drugs, the effects of 1-D nanomaterials that rely solely on photophysical mechanisms are insufficient. Within our group, graphene nano-ribbons (GNRs) have been evaluated for PDT/PTT applications. GNRs exhibit excellent mechanical strength and good biocompatibility and with co-loaded PDT agent can afford potent antibacterial effects comparable to those of antibacterial drugs.102,103 Through our work, we have developed a series of structurally well-defined GNRs functionalised with hydrophilic flexible poly(ethylene oxide) (PEO) chains to reduce the toxicity and improve hydrophilicity.85 GNR-PEO exhibited aqueous dispersion/stability suitable for biological applications. Evaluation of the morphology of these systems revealed hierarchical self-assembled GNR-PEO aggregates as supramolecular nanostrips, which subsequently formed ultralong nanobelts. In addition, the near-infrared (NIR) absorption (750–850 nm) of GNR-PEO permitted its use as PTT agents. PTT was demonstrated in combination with a porphyrin (PDT agent) as a dual wavelength (660 + 808 nm) PDT/PTT therapeutic.103 Specifically, polycationic porphyrin (Pp4N) was mixed in aqueous solution with GNR-PEO2000, which resulted in π–π stacking interactions and formation of a Pp4N/GNR nanocomposite. The positively charged ammonium groups on Pp4N acted as targeting moieties for the negatively charged bacterial surfaces (Fig. 9a). Pp4N/GNR nanocomposite exhibited synergistic antibacterial effects under dual irradiation (660 nm + 808 nm) and was successfully applied for the treatment of A. baumannii and methicillin-resistant S. aureus (MRSA) infected wounds in mouse models (Fig. 9b).
Fig. 9 (a) Basic schematic of the Pp4N/GNR nanocomposite strategy for the light-based treatment (PTT/PDT) of bacteria. (b) Photographs of A. baumannii- and methicillin-resistant S. aureus (MRSA) infected wounds with and without treatment over a 12-day period. Images reprinted with permission from ref. 103. Copyright 2019, Wiley-VCH. |
Fig. 10 (a) Schematic illustration of the preparation procedure of a composite antibacterial agent AQS-GO. (b) SEM images of E. coli incubated with GO and AQS-GO at 0 min and 160 min under dark (D) and visible light irradiation (L). Images reprinted with permission from ref. 112. Copyright 2019, Elsevier B.V. |
The combination of GO with other nanoplatforms results in systems with therapeutic and diagnostic (visualisation) capability. For example, Kim and co-workers have developed a GO-MoS2 nanocomposite film through stacking of 2-D MoS2 (molybdenum disulfide) onto GO.119 This system exhibited a time-dependent therapeutic effect against E. coli, which was visualised using holotomographic (HT) microscopy (Fig. 11). Alternatives to graphene-based materials include graphitic carbon nitride nanosheets, which exhibit antibacterial activities against E. coli, S. typhimurium, S. enteritidis, S. aureus, L. monocytogenes, B. subtilis, and B. cereus.120 The use of such graphitic carbon nitride nanosheets is still at the very early stage of development and as such considerably more research is required to evaluate these systems. In summary, the importance of graphene derivatives for biomedical research is attributed to excellent photothermal conversion efficiency, the capacity to co-load active agents, and the satisfactory biocompatibility. However, graphene systems are difficult to completely disperse in aqueous solutions without modification, meaning that other graphene-like 2-D materials are now being considered for development.
Fig. 11 (a) Schematic illustration of a GO−MoS2 nanocomposite film consisting of 2-D GO and MoS2. (b) Representative cross-sectional images of 3-D RI tomograms of an E. coli bacterial cell in contact with the GO−MoS2 surface for 90 min on the focal plane. Images reprinted with permission from ref. 119. Copyright 2017, American Chemical Society. |
After the emergence of GO, a range of other 2D nanomaterials with properties similar to graphene/GO were developed, which are collectively known as graphene-like platforms and exhibit additional functionality. 2-D MoS2 is a popular graphene-like nanomaterial that has the advantages of graphene and exhibits improved stability/dispersivity. 2-D MoS2 exhibits good structural, physicochemical, optical properties and excellent biocompatibility.121 More importantly, MoS2 can be easily metabolized and decomposed in human bodies and is excreted rapidly, which is a significant improvement when compared to graphene derivatives when considering the body damage or side effects induced by these materials.121 Recently, Niu et al. reported a Gram-selective antibacterial 2-D MoS2 nanomaterial, which achieved selectivity by controlling the light-irradiation time (photomodulation).122 This is of particular significance since providing appropriate treatment for the right bacteria reduces the development of drug-resistant bacteria. As with GO, synergistic studies for the loading of small drug molecules and nanoparticles onto 2-D MoS2 for constructing composites have been performed. A recent report by Ji and co-workers focused on the combination therapy between antibiotics and PTT.123 In this study, ofloxacin (OFLX)-loaded 2-D MoS2 nanoflakes were used as a PTT/antibacterial platform. 2-D MoS2 nanoflakes were modified with electropositive quaternized chitosan (QCS) to improve the aqueous dispersion and act as a targeting moiety for the negatively charged surfaces of bacteria. OFLX-loading on 2-D MoS2 nanoflakes was achieved using π–π stacking and hydrophobic interactions. Remarkably, QCS–MoS2–OFLX proved effective as an antibiotic/PTT agent at low temperatures (45 °C) and low antibiotic concentrations. The effectiveness of the 2-D nanomaterial was demonstrated in vitro and in vivo for the treatment of MRSA (Fig. 12). Nitric oxide (NO) is a known signalling molecule found in the human body with inherent antibacterial properties. These properties are achieved through the known transformation of NO to more harmful reactive nitrogen species (RNS) i.e., peroxynitrite (ONOO−).124,125 Unlike traditional antibiotics, the antibacterial properties of NO are not dependent on the type of bacteria and in addition it is known to promote wound healing. Gu and co-workers rationalised that the use of a 2-D nanomaterial would facilitate the effective delivery of NO (nanovehicle) and improve the therapeutic effects against bacteria. As a result, α-CD modified 2-D MoS2 nanosheets were assembled with the heat sensitive (NO) donor N,N′-di-sec-butyl-N,N′-dinitroso-1,4-phenylenediamine (BNN6).126 NIR light irradiation (808 nm) activated PTT and generated NO. The antibacterial effects were successfully demonstrated using infected mouse models.
Fig. 12 (a) Schematic illustration of the preparation of QCS–MoS2–OFLX for the treatment of methicillin-resistant S. aureus (MRSA). (b) Methicillin-resistant S. aureus-infected wounds in mouse cut models after different treatments of PBS (control), QCS–MoS2, QCS–MoS2–OFLX, and ofloxacin (OFLX) with and without 808 nm NIR irradiation at day 7. Bacteria were separated from the corresponding wounds and plated on nutrition culture medium. Images reprinted with permission from ref. 123. Copyright 2020, Tsinghua University Press and Springer. |
2D MoS2 has been used for loading nanoparticles, in combination with AgNPs and D-Cys for the construction of an effective antibacterial nanocomposite.127 More recently, a multifunctional nanomaterial was developed consisting of 2-D MoS2 nanosheets and AgBr nanoparticles (AgBr@MoS2) grown on Ti-based implant materials; the AgBr was co-loaded to reduce the inherent toxicity. Visible light irradiation (660 nm) of the nanomaterial resulted in significant phototherapeutic efficacy against E. coli and S. aureus.128 2-D Ti3C2Tx MXene nanosheets have emerged as an attractive nanomaterial for biomedical applications.129 In 2016, Ti3C2Tx MXene nanosheets were evaluated for their antibacterial properties and compared with GO. Significantly better antibacterial effects were observed when compared to those of GO (∼2–4 fold greater) against both E. coli and B. subtilis.130 As with graphene, SEM and TEM images revealed physical damage to the cell membrane and biological assays identified the induction of oxidative stress. The authors anticipate that MXenes will find use in biofouling and bactericidal applications due to the good biocompatibility. Recently, Zhang and co-workers used the known low-cost and biocompatible semi-conductor material, Sb2Se3 for the development of an antibacterial nanomaterial.131 In this report, polyvinylpyrrolidone (PVP)-capped Sb2Se3 was used for the treatment of bacteria including E. coli and methicillin-resistant S. aureus (MRSA) in vivo. 2-D tungsten disulfide (WS2) nanomaterials have been explored for water filtration applications, exhibiting excellent antibacterial properties against S. aureus and E. coli.132 More recently, Pramanik and co-workers developed a combined 2-D and 0-D nanomaterial strategy for the identification of antibiotic-resistant bacteria.133 This was achieved through the construction of WS2–AuNPs and using the surface enhanced Raman spectroscopic properties of AuNPs enabling the rapid detection (90 min) of MDR Salmonella DT104. Ikram and co-workers have reported Zr-doped MoS2 nanosheets for catalytic and antibacterial applications.134 These systems were effective against E. coli and S. aureus through the catalytic generation of ROS. This catalytic-based antibacterial approach was then further elucidated by Yin and co-workers by directly loading enzymes onto 2-D MoS2. They reported lysozyme-coated MoS2 nanosheets (Lys-MoS2), which displayed good antibacterial efficacy against Gram-negative E. coli and Gram-positive B. subtilis.135 This was due to synergistic effects between the lysozyme and peroxidase activity of the MoS2 nanosheets.
Often medical implants are prone to bacterial infection; for this reason, Wu and co-workers developed a chitosan@MoS2 nanocomposite to overcome this problem. Chitosan@MoS2 was deposited onto medical Ti-based implants through an electrophoretic deposition method.136 Upon dual-light irradiation of chitosan@MoS2-Ti (660 nm and 808 nm), significant bacterial inhibition was observed in vitro and in vivo. Moreover, 2-D MoS2 could be combined with graphene derivatives. PEG-2-D MoS2/rGO therapeutic nanoflakes were developed by Li and co-workers and loaded with a streptomycin sulfate (SS) antibiotic. In combination with NIR light irradiation, the therapeutic efficacy of PEG-MoS2/rGO-SS was significantly enhanced and a synergistic therapeutic effect was observed between SS and light-based therapy.137 Black phosphorus (BP) is an emerging 2-D nanomaterial used for semiconductor applications. Aksoy and co-workers reported BP/AuNP nanocomposites for antibacterial applications with good biocompatibility.138 The NIR laser irradiation (808 NM) of these nanocomposites resulted in the PTT/PDT treatment of planktonic bacteria and biofilm-based E. faecalis (Fig. 13a). Live/dead staining and fluorescence imaging were used to evaluate the therapeutic efficacy of the BP/Au nanocomposites against E. faecalis (Fig. 13b). For more examples of nanomaterials beyond graphene (NBG), the reader is directed to an excellent review by Yin and Gu.106
Fig. 13 (a) Schematic illustration of the construction process of a black phosphorus- and AuNP-based nanocomposite BP/Au and its effects in treating bacteria upon NIR irradiation. (b) Fluorescence images of E. faecalis cells after live/dead staining with different treatment protocols. Images reprinted with permission from ref. 138. Copyright 2020, American Chemical Society. |
Fig. 14 (a) Schematic illustration of the preparation of an antibacterial polymer scaffold based on mesoporous bioactive glass (MBG). (b) E. coli inhibition rings and inhibition rates of PLLA-PGA/MBG (1), PLLA-PGA/2Ag@pMBG (2), PLLA-PGA/4Ag@pMBG (3), PLLA-PGA/6Ag@pMBG (4), and PLLA-PGA/8Ag@pMBG (5) after 24 h of culture. Images reprinted with permission from ref. 145. Copyright 2020, Elsevier B.V. |
Ag-decorated polydopamine/mesoporous silica composites were constructed to enhance the therapeutic efficiency of Ag and reduce toxicity via an incorporating/releasing effect triggered by pH changes and ROS, and was used for the treatment of drug-resistant bacteria and tumor cells.148 Mesostructured cellular silica foams (MCF) were demonstrated by Xia and co-workers as excellent antibacterial hemostatic agents.149 Metallic glass consisting of Mg, Ag, and Cu has been reported by Wang and co-workers for the long-term treatment of S. aureus and E. coli with the sustainable release of Cu and Ag ions.150 Compared with all the individual components, this system was shown to perform significantly better due to synergistic effects. Other strategies include the development of 3-D-based graphene derivatives for antibacterial applications. For example, tannic acid was used to reduce GO and induce self-assembly to form a graphene hydrogel,151 which represents an environmentally-friendly, and cost effective approach to treat both S. aureus and E. coli. The 3-D graphene exhibited high porosity, low density, hydrophobicity, good mechanical performance and thermal stability compared with normal 2-D graphene, with the ability to adsorb a range of oils, dyes and organic solvents. These results exhibited promise for water purification applications with the ability to treat S. aureus and E. coli.152 Bahadur and co-workers developed a 3-D layered double nanohybrid consisting of Mg–Al layered double hydroxide-reduced GO (rGO). The synergistic antibacterial effect observed against E. coli was much better than those for the individual components with enhanced selectivity, which was attributed to protein degradation and GSH loss through the induction of oxidative stress.153 Moreover, a vertical heterostructure consisting of MoS2-coated rGO was developed by Yu and co-workers using a microwave-assisted hydrothermal method, which exhibited in situ bacterial binding with enhanced nanozyme activity and producing ROS for excellent E. coli/S. aureus antibacterial effect.154 The overall effects observed within the heterostructure were synergistically improved compared with those of single MoS2 or rGO. The mechanism was relevant for the catalytic generation of a range of ROS including hydroxyl radicals (OH˙) from H2O2 by the nanozyme upon light activation, making the system suitable for use in mouse wound-infection models.
Huang and co-workers reported a degradable 3-D-printed polylactic acid (PLA) scaffold for applications in bone tissue engineering.155 The PLA scaffold was elaborated around a 3-D-printed core functionalized with an adherent polydopamine coating, and the modified scaffold was then used to immobilize a mixture of gelatin, needle-like nanohydroxyapatite (nHA), and ponericin (Fig. 15a). Long-term antibacterial activity was observed towards E. coli and S. aureus (Fig. 15b). Zheng and co-workers developed AgNP-associated carbon aerogels p-BC/AgNPs for antibacterial applications.156 p-BC/AgNPs exhibited excellent antibacterial efficiency against E. coli and S. aureus, which was better than with just AgNPs and p-BC. Moreover, p-BC/AgNPs exhibited excellent cell attachment and biocompatibility. Due to these properties, the authors proposed that this newly developed antibacterial material could be used for wound dressings, medical implants, and drug release applications.
Fig. 15 (a) Schematic illustration of a composite 3-D-printed polylactic acid (PLA) scaffold. (b) Antibacterial effects of the ponericin-modified scaffold against E. coli and S. aureus at different ponericin concentrations. Images reprinted with permission from ref. 155. Copyright 2017, American Chemical Society. |
Despite the many successful experiments demonstrating the use of these systems, their use for clinical applications still represents a major hurdle due to their instability and potential side-toxicity in vivo. As such this has significantly prevented their development into commercially available therapeutics, which is further exemplified by the scarcity of functional materials being evaluated in vivo.162 However, the most recent in vivo studies have demonstrated excellent therapeutic efficacy without any serious toxicity being observed. Possible methods for enhancing biocompatibility may include functionalisation of the nanomaterial platforms with carbohydrates and peptides to afford targeted systems. Furthermore, these biomolecules may provide additional antibacterial properties. A representative example is polymeric antimicrobial peptides (AMPs) that have been recently developed by Liu and co-workers,163–165 which are cationic163,164 and amphiphilic165 and exhibit antifungal activity,163 immunomodulatory functions,165 and significant time-resolved effects against multiple bacterial species and biofilms both in vivo and for mouse infection models. In the near future, nanomaterials emerging from the developments in materials science, will result in improved clinically relevant properties such as stability, biocompatibility, and biodegradability, and result in more tissue-friendly targeting/assisting agents. With this review we have summarized the current state of the art for nanomaterial-based antibacterial systems and provided guidelines for the development of new and improved nanomaterial platforms. We are confident that with sustained hard work in this area,166 an antibacterial nanomaterial system could soon be available to treat patients with MDR infections.
E. coli | Escherichia coli |
S. aureus | Staphylococcus aureus |
MRSA | Methicillin-resistant S. aureus |
P. aeruginosa | Pseudomonas aeruginosa |
S. epidermidis | Staphylococcus epidermidis |
P. gingivalis | Porphyromonas gingivalis |
P. micros | Peptostreptococcus micros |
P. intermedia | Prevotella intermedia |
S. mutans | Streptococcus mutans |
B. subtilis | Bacillus subtilis |
A. baumannii | Acinetobacter baumannii |
S. faecalis | Streptococcus faecalis |
E. cloacae | Enterobacter cloacae |
B. pertussis | Bordetella pertussis |
C. albicans | Candida albicans |
K. pneumoniae | Klebsiella pneumoniae |
P. mirabilis | Proteus mirabilis |
S. marcescens | Serratia marcescens |
DDS | Drug delivery system |
PDT | Photodynamic therapy |
PTT | Photothermal therapy |
Ag | Silver |
Ti | Titanium |
Cu | Copper |
Pd | Palladium |
Se | Selenium |
ROS | Reactive oxygen species |
0-D | Zero-dimensional |
1-D | One-dimensional |
2-D | Two-dimensional |
3-D | Three-dimensional |
GQDs | Graphene quantum dots |
AgNPs | Silver nanoparticles |
NCC | Nanocrystalline cellulose |
D-Cys-AgNPs | D-Cysteine functionalised AgNPs |
EPS | Extracellular polymeric substances |
D-Cys | D-Cysteine |
Bi | Bismuth |
BiNPs | Bismuth nanoparticles |
γ-CD | γ-Cyclodextrin |
MOFs | Metal–organic frameworks |
GRGDs | Gly-Arg-Gly-Asp-Ser |
PVA | Poly(vinyl alcohol) |
CNDs | Carbon nanodots |
OD | Optical density |
MC3T3-E1 cells | Mouse embryo osteoblast precursor cells |
CA | Citric acid |
CDs | Carbon dots |
GO | Graphene oxide |
TEM | Transmission electron microscopy |
SEM | Scanning electron microscopy |
AuNPs | Gold nanoparticles |
DAPT | 4,6-diamino-2-pyrimidinethiol |
DGNPs | (4,6-Diamino-2-pyrimidinethiol)-modified gold nanoparticles |
uDGNPs | Ultrasmall DGNPs |
MOF@CeO2NPs | CeO2-decorated nanoparticle MOFs |
ATP | Adenosine triphosphate |
Ce | Cerium |
Zr | Zirconium |
MEH-PPV | 2-Methoxy-5-((2-ethylhexyl)oxy)-p-phenylenevinylene |
BFPB | 4-{2,2-Bis[(4-formylphenoxy)methyl]-3-(4-formylphenoxy)propoxy}benzaldehyde |
TMB | 3,3′,5,5′-Tetramethylbenzidine |
CEMA | 2-Chloroethyl methacrylate |
HEMA | Hydroxyethyl methacrylate |
SWNTs | Single-walled nanotubes |
MWCNTs | Multi-walled carbon nanotubes |
PES | Polyethersulfone |
UF | Ultrafiltration |
GNRs | Graphene nanoribbons |
PEO | Poly(ethylene oxide) |
NIR | Near-infrared |
Pp4N | Polycationic porphyrin |
AgNWs | Nanowires |
4MPFG | N,N-Bis(pyridyl-4-methyl)-N-fluorenyl-9-methoxycarbonyl (Fmoc)-L-glutamate |
HBTC | 1,3,5-Benzenetricarboxylic acid |
AuNRs | Gold nanorods |
MMO | Mixed metal oxide |
rGO | Reduced GO |
AgNP–NA–rGO | AgNP/sodium 1-naphthalenesulfonate-functionalized reduced graphene oxide |
AQS | Anthraquinone-2-sulfonate |
PEG | Polyethylene glycol |
MoS2 | Molybdenum disulfide |
HT | Holotomographic |
MDR | Multidrug-resistance |
QAS | Quaternary ammonium salt |
NBG | Nanomaterials beyond graphene |
RI | Refractive index |
SS | Streptomycin sulfate |
OFLX | Ofloxacin |
QCS | Quaternized chitosan |
NO | Nitric oxide |
RNS | Reactive nitrogen species |
ONOO− | Peroxynitrite |
BNN6 | N,N′-Di-sec-butyl-N,N′-dinitroso-1,4-phenylenediamine |
Lys-MoS2 | Lysozyme-coated MoS2 nanosheets |
PVP | Polyvinyl pyrrolidone |
WS2 | Tungsten disulfide |
BP | Black phosphorus |
COFs | Covalent organic frameworks |
MBG | Mesoporous bioactive glass |
pMBG | Self-polymerization mesoporous bioactive glass |
PGA | Polyglycolic acid |
ZIF | Zeolitic imidazolate framework |
NCS | Nanocube-like structure |
MCF | Mesostructured cellular silica foam |
GSH | Glutathione |
OH˙ | Hydroxyl radicals |
PLA | Polylactic acid |
nHA | Needle-like nanohydroxyapatite |
AMPs | Antimicrobial peptides |
Footnote |
† Equal contribution. |
This journal is © The Royal Society of Chemistry 2021 |