Recent advances in gold nanoparticle-based targeted photodynamic and photothermal cancer therapy

Abstract

Cancer, the second leading cause of death worldwide, remains a major threat to human health. Current treatment options include surgery, radiation therapy, and chemotherapy and these options have significantly improved patient survival. However, they are often associated with severe side effects and high-risk of recurrence. Consequently, there is an urgent need for more effective and less invasive therapeutic strategies. Light-mediated tumor ablation techniques, such as photodynamic therapy (PDT) and photothermal therapy (PTT), have emerged as promising non-invasive approaches with notable potential in cancer management. Recent advances in nanomedicine, particularly the integration of photosensitizers (PS) with nanoparticles, have further enhanced the diagnostic and therapeutic efficacy of these modalities. Among various nanomaterials, gold nanoparticles (AuNPs) have attracted considerable attention due to their tunable optical properties, biocompatibility, and ability to mediate both PDT and PTT through controlled light irradiation and localized hyperthermia. In this review, we highlight recent progress in AuNP-based strategies for targeted photodynamic and photothermal therapies, discuss their current clinical status, and outline key challenges that must be addressed to facilitate successful translation from laboratory research to clinical practice.

---

1. Introduction

Given that cancer is the second leading cause of death globally, it is one of the most prevalent and worldwide health issues.¹ Conventional cancer therapies, however, have significant disadvantages and often don't provide adequate outcomes.^2,3 Patients often need considerable time to recover from side effects after standard cancer treatment.⁴ Furthermore, the majority of techniques are not very successful in killing cancer cells, and cancer chemotherapy may lead to problems with the heart, kidneys, bladder, neurological system, and lungs, among other organs.⁵ Recently, there has been a lot of interest in using nanotechnology to detect and treat tumor illnesses;⁶ this is because nanotechnology may provide novel approaches for investigating and regulating a wide range of biological and medical processes;⁷ as a result, there are great hopes for developing novel methods to revolutionize cancer detection and therapy.⁸ Many types of nano-objects of biological importance are now being used, such as liposomes, micelles, polymer nanoparticles, and metal nanoparticles.^9,10 Out of them, nanoparticles have the greatest potential for use in many medical applications.¹¹ This is shown by their practical usage as delivery agents, image-enhancing sensors, and diagnostic agents.¹² Furthermore, when combined with other therapies, the usage of nanoparticles may improve their effectiveness.¹³

A novel treatment approach for cancer with nanotechnology proposes gold nanoparticles, which are potential nanoproducts for cancer treatment. Due to their distinct optical and physicochemical characteristics, gold nanoparticles (AuNPs) have enormous potential for use in theranostics, medicine, and diagnostics. These nanoparticles may be functionalised for use in biological applications; their size and shape are often adjustable.^14,15 Gold nanostructures are used as drug carriers in therapies to reduce off-target effects and enable focused delivery to illness locations.¹⁶ AuNPs' surface chemistry has proven beneficial in attaching targeting molecules, imaging tags, and medicinal compounds for various purposes, particularly as a delivery mechanism.^17,18 Photothermal therapy (PTT), a well-known use of AuNPs, has become a significant therapeutic area for cancer treatment because of its noninvasiveness, low cost, and minimal side effects.¹⁹ AuNPs' surface electrons are stimulated and resonate when exposed to near-infrared radiation (NIR); this results in the rapid conversion of NIR light into heat and, eventually, a rise in the cancer cell's temperature to between 41 and 47 °C because of surface photo resonant peaks.²⁰ As a consequence, the cell sustains irreparable damage, including denaturation of proteins and membrane disruption.²¹ According to Alle et al. (2020), one benefit of using AuNPs in PTT is that they may be easily administered to the local tumor location while limiting non-specific dispersion. They can be tuned to build a multifunctional cancer PTT and medication delivery system.²²

Using AuNPs in photodynamic therapy for cancer treatment is an additional therapeutic benefit. PDT has been identified as a potential early-stage tumor when surgery is not feasible and contributes to cancer patients' longer lives.²³ PDT is an affordable, repeatable procedure that aids the tumor's long-term care.²⁴ PDT produces singlet or reactive oxygen species, which are hydrophobic light-sensitive chemicals that destroy cancer cells it is known that AuNPs increase PS photosensitizing capabilities, maybe due to the metal's localized surface plasmon resonance (LSPR). As a result, AuNPs may raise the PS PDT efficiency.²⁵ Research revealed that AuNPs might stimulate a PDT and PTT impact that effectively killed cancer cells.²⁰

This review will focus on the advancements of gold nanoparticles in targeted photodynamic and photothermal therapy; thus, this review article is divided into seven pieces. Section 1 provides a concise explanation of the study's beginning. Section 2 covers the essential principles of photodynamic therapy and photothermal therapy. The role of nanotechnology in photodynamic therapy and photothermal therapy is explained in Section 3, while gold nanoparticles are covered in Section 4. The use of gold nanoparticles in photothermal and photodynamic treatment is covered in Section 5. The study also briefly discusses the clinical trial status of gold nanoparticle (AuNPs)-mediated photodynamic therapy (PDT) and photothermal therapy (PTT) in Section 6. The challenges associated with gold nanoparticles for medication delivery systems are covered in Section 7. The future perspectives are briefly described in Section 8.

2. Essential principles of photothermal therapy and photodynamic therapy

Phototherapies are a fast-growing class of cancer treatments that use different wavelengths of light to cause photothermal or photochemical changes in a target tissue.²⁶ The two most popular phototherapies are PDT and PTT. To create deadly reactive oxygen species (ROS) or increase the ambient temperature, they use light and either endogenous or exogenous absorbers.²⁷ PDT and PTT can supplement traditional cancer therapies because of their unique action methods. Both phototherapies have overcome compensatory signaling pathways and chemotherapeutic resistance at the cellular level.^28–30 PDT and PTT may improve tumor medication delivery.^31–33 Furthermore, PDT and PTT reduce off-target toxicity because they provide greater spatiotemporal control than systemic treatments. Modern endoscopic and fiberoptic light delivery methods allow for the minimally invasive irradiation of a wide range of solid tumors, including those in anatomically delicate locations that may not be amenable to surgery.^27,34 Lastly, compared to radiation treatment, phototherapies use nonionizing radiation, which lowers the chance of developing secondary cancer.^27,34

2.1 Photothermal therapy (PTT)

PTT is a potentially useful therapeutic method that uses photothermal materials to generate heat from light energy.³⁵ This heat may specifically destroy cancer cells. By varying the photothermal materials' concentration and size, as well as the intensity and duration of light exposure, it is possible to regulate the heat produced by these materials accurately; this targeted therapy, which may be carried out using non-invasive light sources, may lessen the risk of damage to healthy tissues, making the treatment less invasive.^36,37 PTT also offers several benefits, such as high specificity and selectivity, which enable accurate targeting of cancer cells.³⁸ To improve treatment results, it may be used with various therapeutic modalities.^39,40 Two essential elements for a successful PTT process are a photothermal nanoagent (PTA) that may induce photothermal effects and near-infrared light (NIR) that has good tissue penetration.⁴¹ During PTT, PTA is initially given intravenously or by other means, and since solid tumors have an elevated penetration and retention effect (EPR), PTA preferentially builds up in the tissue of the tumor. The tumor tissue is then exposed to a high-penetration NIR laser. PTA quickly raises the tumor's local temperature to a point where tumor cells perish by absorbing certain NIR wavelengths and converting them into heat energy via nonradiative decay.^42,43 The photothermal conversion efficiency of PTAs is a major factor in PTT efficacy. To get the best PTT results, it is thus essential to produce PTAs with significant NIR light absorption and high photothermal conversion efficiency. Additionally, PTAs with strong biocompatibility, the capacity to accumulate in tumor tissues specifically, and biodegradability are necessary for clinical use.^44,45 Fig. 1 shows the mechanism of action of photothermal therapy.

Fig. 1 Mechanism of photothermal therapy. A schematic of the mechanism of action of photothermal therapy, reprinted from ref. 53, copyright 2022, Elsevier.

2.2 Photodynamic therapy

PDT is a unique kind of light therapy that depends on the interaction of three essential elements: light, molecular oxygen (MO), and photosensitiser (PS)⁴⁶ (Fig. 2). Lamps, lasers, and light-emitting diodes are the three main light sources used by PDT. The choice of light source is influenced by the target's location, the photosensitizer's absorption spectrum, and the necessary dosage.⁴⁷ Because the oxygen molecules in the surrounding environment work as electron carriers, the non-toxic photosensitising substance that was applied to the target region gets activated when it is subjected to the appropriate amount of light.^48–50 This leads to the production of toxic reactive oxygen species (ROS), which break down cell membranes and cause necrosis or apoptosis in target tissues and microorganisms.^51,52

Fig. 2 Mechanism of photodynamic therapy. A schematic of the mechanism of action of photodynamic therapy, reprinted from ref. 54, copyright 2021, Springer Nature.

3. Nanotechnology

Nanotechnology is the study of atomic, molecular, and supramolecular molecules to find properties that could be used to enhance human health. Modern biology and medicine are evolving with nanotechnology to produce novel materials at the nanoscale that may be used in biological systems.^55–57 Nanotechnology employs concepts and methodologies at the nanoscale to understand biosystems.⁵⁸ Because of their special qualities, nanoparticles are employed in medical applications.^59,60

One of the primary benefits of using nanoparticles for cancer diagnostics is their increased ratio of surface area to volume in comparison to bulk materials^61–63 this property makes it possible to identify certain cancer compounds by densely coating the surfaces of nanoparticles with antibodies, small molecules, and other moieties.^63–65 Nanoparticles have several fortunate benefits. They have multiple uses, including delivering hydrophobic compounds, actively and passively targeting disease cells, and extending the time a drug is in circulation.^66–68

3.1 Role of nanotechnology in photothermal therapy

Targeting the malignant region with a photothermal substance to selectively heat it and produce thermal damage to the tumor is known as photothermal therapy, a safe and efficient cancer treatment. These photothermal agents may be natural chromophores, metal nanoparticles, or light-absorbing dyes like porphyrin coupled with a transition metal, naphthalocyanine, or indocyanine green. Electromagnetic radiation, such as microwaves and radiowaves, damages cells in the thermal treatment of malignancies by denaturing proteins and membranes, ultimately leading to cell death. Since tumor cells are heat-sensitive, photothermal treatment selectively targets them without affecting healthy cells.⁶⁹ Drug-carrying nanoparticles, for example, are photothermal agents because they absorb light and produce heat.⁷⁰ The NIR region has high absorption of gold nanoparticles, carbon nanotubes (CNTs), and nanorods between 650 and 900 nm.⁷¹ Nanoparticles in a size range of 10–100 nm have the ability to transform light into heat, which means they can give less energy needed to destroy tumor cells.^48,72 In addition to the death of cells mediated by heat, heating metal nanoparticles, such as gold nanoparticles, results in bubbles and cavitation around the nanoparticle, often producing mechanical stress that eventually damages cells.⁷³ Because the targeted tumor cells in nanoparticle-mediated photothermal treatment are optically sensitive, a lower threshold laser is needed to increase the heat around the infected cells to a level sufficient to cause cellular damage. When anti-EGFR antibody-linked gold nanoparticles were utilized in photothermal cancer treatment, researchers discovered that the resulting 70–80 °C thermal abrasion was what killed the cells.⁶⁹

3.2 Role of nanotechnology in photodynamic therapy

Due to its ability to administer PS precisely to specific locations with little harm to normal tissues, PDT's use of nanotechnology has opened up new therapeutic options for cancer.⁷⁴ Much research has been done recently on integrating NPs and PSs to address the underlying problems with traditional PDT.⁷⁵ Because of their innate hydrophilicity, NPs may greatly increase PSs' solubility in water, increasing their cellular absorption.⁷⁶ Because NPs may get past immune system barriers and prolong the release of conjugated PSs, they shield them from unintended destruction.⁷⁷ Moreover, because of their high surface area-to-volume ratio, they can hold a lot of anticancer medications in cancer tissue.⁶⁸ Because of the EPR effect, small NPs may easily enter cancer cells.⁷⁸ Excellent biocompatibility, highly changeable surface chemistry, and versatility in loading different drugs and targeting agents for different goals are other advantages of NPs that have led to their acceptance as a PDT alternative.⁷⁹ Through the EPR effect, NPs have enhanced the pharmacokinetic characteristics of PDT, including high volumes of distribution, excellent clearance values, and increased bioavailability in cancer cells.⁸⁰ As a result, NP-based drug delivery methods in PDT are gaining traction quickly. The role of different types of nanoparticles in photothermal and photodynamic therapy is shown in Fig. 3, and various Nanotechnologies used in Photodynamic Therapy and Photothermal Therapy are listed in Table 1.

Fig. 3 The role of nanotechnology in photothermal and photodynamic therapy. [a] Schematic synthesis of MoS₂@RP heterostructure for synergistic PDT/PTT of ccRCC, reprinted with permission from ref. 81, Copyright 2024 Elsevier; [b] schematic representation of PSBTBT-Ce₆@Rhod NPs-mediated PLD-activatable tumor images and combined PTT/PDT therapy reprinted with permission from ref. 82, Copyright 2021 ACS; [c] schematic illustration of the preparation of HSA-AETHB NPs and PTT/PDT synergic therapy of tumors. Reprinted with permission from ref. 83, Copyright 2019 American Chemical Society; and [d] schematic illustration of the preparation of HPCOF and photoacoustic imaging-guided combined therapy under 660 nm and 808 nm laser irradiation. Reprinted with permission from ref. 84, Copyright 2024 Elsevier.

Table 1 Various nanotechnologies used in photodynamic therapy and photothermal therapy

Nanocomposite	Modality & protocol	Cancer type	Outcomes
PEGylated GO modified by folic acid, rhodamine B	PTT and PDT	In vivo Ehrlich tumors cells	Using the theranostic function, temperature change via GO/FA-ICG to 40 °C suppressed tumour growth^85
	808 nm, 1.8 W cm^−2
Multifunctional graphene oxide	PTT and PDT	MCF-7 cells	When photothermal and photodynamic therapy were combined, the cancer cells were eradicated more effectively than when they were treated separately^86
	808 nm, 660 nm, 2 W cm^−2
Hollow silica nanoparticles loaded with hydrophobic phthalocyanine (Pc@HSNs)	PTT and PDT	Tumor-bearing mice (in vitro and in vivo)	Both in vitro and in vivo studies shown that the dual phototherapeutic activity of Pc@HSNs may eliminate cancer cells or tumour tissues^87
	730 nm, 1.5 W cm^−2 for 10 min
Mesoporous silica composite nanoparticles (hm-SiO2(AlC4Pc)@Pd)	PTT and PDT	HeLa cells (in vitro)	Results in vitro demonstrated that combination PDT/PTT therapy using hm-SiO2(AlC4Pc)@Pd had a higher cell-killing efficacy than either PDT or PTT treatment alone after exposure to a 660 nm CW-NIR laser^88
	660 nm 0.5 W cm^−2 for 7 or 10 min
Poly(cyclotriphosphazene-co-tetraphenylporphyrin-co-sulfonyldiphenol) nanospheres (CP-TPP)	PTT and PDT 808 nm laser (1.5 W) and 630 nm LED (50 mW cm^−2) for 8, 15, and 20 min	HeLa cells (in vitro)	Cell viability was lower than that of individual PDT or PTT at doses of CP-TPP/Au/PEG nanospheres between 10 and 100 μg mL^−1 (ref. 89)
Self-assembled zinc phthalocyanine nanoparticles	PTT and PDT 650 nm 0.7 W cm^−2, 10 min	HeLa cells (in vitro)	Nearly 93% of the HeLa cells were killed by the synergistic PTT and PDT at a particle concentration of 20 μM after ten minutes of laser therapy^90
Carbon nanohorn/phthalocyanine hybrid	Synergistic PTT and PDT 650 nm laser (3 W cm^−2)	HeLa cells (in vitro)	The cell viability test indicates that the combination of PTT and PDT exhibits much greater cell-killing efficacy in vitro^91
Phycocyanin–polypyrrole nanoparticles	Synergistic PDT and PTT 620 nm (100 mW cm^−2) and 808 nm (2 W cm^−2) for 10 and 5 min	MDA-MB-231 human breast cancer cells and HEK-293 human embryonic kidney cells	The obtained nanoparticles effectively killed MDA-MB-231 cells in a dual way upon laser illumination^92
Black phosphorus quantum dots (BPQDs)	Synergistic PTT and PDT 625 nm light (80 mW cm^−2) for 10 min 808 nm laser (2 W cm^−2) for 2 min	Hep G2 cells	The results demonstrate that combined phototherapy significantly promotes the medicinal effectiveness of cancer therapy compared to PTT or PDT alone^93
Nanographene oxide	Synergistic PTT and PDT 808 nm, 655 nm, 2 W cm^−2, 3 min	Hela and NIH/3T3 cells	The combined effect of PDT and PTT treatment of the cells led to a much higher rate of cell death in comparison to PDT-only or PTT-only therapy^94
Pluronic-based graphene oxide-methylene blue nanocomposite	Synergistic PTT and PDT 660 nm LED light and 808 nm NIR light at 0.5 W cm^−2	Cervical cancer (SiHa) cells	The results indicated that the nanocomposite had the potential to treat cancer via non-invasive phototherapy effectively^95
Nano-graphene oxide	Synergistic PTT and PDT 808 nm (320 mW cm^−2; 15 min) and 980 nm (320 mW cm^−2; 18 min)	B16F0 cells	Experiments conducted in vitro shown that B16F0 melanoma cancer cells may be effectively destroyed by phototherapy when exposed to 980 nm light, thanks to the combination of GO-mediated PTT and PDT effects^96
Iron oxide carbon dot (Fe3O4-CDs) nanoparticles	Synergistic PTT and PDT 660 nm laser (0.5 W cm^−2) and 808 nm laser (2 W cm^−2)	HeLa cells	Because of the complementary PTT and PDT using a near-infrared laser, conducted both in vitro and in vivo demonstrated that GP-PGA-Fe3O4-CDs@BPQDs were extremely biocompatible and had outstanding tumor-inhibition effectiveness^97

---

3.3 Drug targeting mechanisms in nanotechnology

Passive targeting and active targeting are the two types of medication targeting mechanisms. The underlying causes of increased permeability and retention (EPR) based medication targeting in passive targeting include the tumors' faulty lymphatic drainage and quickly expanding leaky vascularization, which helps to retain nanoparticles and submicron particles.⁹⁸ For this particular kind of cancer treatment, nanoscale drug carriers such as liposomes, dendrimers, and inorganic nanoparticles are being thoroughly researched in terms of drug delivery.⁹⁹ Owing to their small size, these nanoparticles preferentially aggregate at the tumor site via their enhanced permeability receptor action, allowing them to pass through hyper-permeable blood capillaries.¹⁰⁰ The interaction of a ligand-containing drug carrier with target cell surface receptors is the main mechanism of the active targeting technology. This process facilitates intracellular drug accumulation by receptor-mediated endocytosis and tumor accumulation of the drug.¹⁰¹ Typically, ligand-functionalized nanoparticles may actively target one or more specific receptors that are overexpressed in tumor cells. As a result, endothelial cells and tumors are identified using cellular targets in an active targeting technique.^102,103 Drug targeting mechanism are shown in Fig. 4.

Fig. 4 Drug targeting mechanism [a] schematic representation of PTT-mediated passive targeting and active targeting of tumor cells via inorganic NCs in the management of melanoma, reprinted with permission from ref. 104 Copyright 2024 Elsevier; [b] description for delivery of the NPs into the body followed by the tumor-specific accumulation of the NPs because of the EPR effect (passive targeting), reprinted with permission from ref. 105, Copyright 2023 Elsevier; [c] dual-targeted delivery of Dox-DNFs and BSA-AuNPs for combinational chemo-photothermal therapy of cervical cancer, reprinted with permission from ref. 106, Copyright 2023 Elsevier; and [d] structural composition and the proposed mechanism of action of VES/DOX·HCl co-delivered nanovesicle PEBP-VES-D-Ps based on amphiphilic poly[(PEG)_x(BIMA)_yphosphazene]_n (PEBP) for MDR reversal, reprinted with permission from ref. 107, Copyright 2021 Elsevier.

4. Gold nanoparticles

Due to its crucial resonance features, gold nanoparticles are gaining interest as potential uses in cancer treatment. Gold nanoparticles' wavelengths, emission frequencies, and aggregation state strongly depend on their size, shape, surface, and aggregation state. These particles occur in different sizes and forms, including nanoporous gold disks, nanoporous gold cages, nanoflowers, nanoshells, nanospheres, and nanorods, as illustrated in Fig. 5. Each nanoparticle has a distinct wavelength representing its electrons' maximal excitation. Gold nanoparticles can absorb and scatter incident light simultaneously, and “photon confinement” produces powerful electromagnetic fields that cause a variety of visual phenomena on the particle surface.¹⁰⁸

Fig. 5 Different types of gold nanoparticles for photothermal and photodynamic therapy. Created in BioRender. Dhilip Kumar, S. (2025) https://BioRender.com/7k1a6dq.

Numerous varieties of gold nanoparticles have been investigated recently. Factor like wavelength energy absorbance should be considered when comparing the photothermal heating capability of each kind of particle. Each form of gold nanoparticle has unique benefits and characteristics; it is impossible to determine which type is most appropriate for treating cancer, given these differences in size. Consequently, choosing gold nanoparticles with benefits for every application is crucial. However, the observed patterns support the size impact of photothermal heating and are consistent with experimental results.¹⁰⁹ A comparative study on various gold nanoparticles-mediated photothermal and photodynamic therapy is listed in Table 2.

Table 2 Comparative study on various gold nanoparticles-mediated photothermal and photodynamic therapy

Type of gold	Laser treatment	Cell model	Application	Outcomes	Advantages
Gold nanorods	808 nm laser (0.5 W cm^−2), 60 s	Human liver cancer HepG2 cells	PTT	When more MMP-9 was added, the ensuing responsive AuNRs displayed much greater cellular uptake in vitro^136	Experimentally, AuNRs are effective cancer treatments because they penetrate and retain tumour tissue better than normal tissue. The aspect ratio of AuNRs influences tumour retention. Despite the fact that smaller AuNRs are eliminated faster, high aspect ratio and small volume AuNRs are ideal for tumour-mediated transport employing the EPR effect. AuNRs circulate longer than nanospheres, and macrophages absorb them four times better^137,138
Gold nanorods	633 nm and 808 nm	Rats, 8 to 10 weeks in age	PDT & PTT	The combination of PDT + PTT therapy caused a significant reduction in tumor volume and large-area tumor necrosis^139
Gold nanocages	805 nm	The breast cancer cell line SK-BR-3	PTT	We have shown that Au nanocages with comparable optical characteristics may effectively act as agents for the in vitro photothermal killing of cancer cells^140	Photothermal conversion is enhanced by gold nanocages, a novel nanoparticle. The average size is 20–50 nm. A galvanic replacement reaction with a silver template and gold salt creates a hollow gold–silver alloy structure with variable wall thickness. The nanocage's surface develops a gold coating due to the metals' differing chemical potentials, while silver ions dissolve into the aqueous HAuCl4 solution. Gold nanocages' porous surface and hollow interior make them promising for medication delivery and encapsulation. Gold nanocages passively and actively distribute medications by upregulating cancer cell receptors and increasing EPR^141
Gold nanocages	580 and 630 nm 2.5 W cm^−2	HeLa cells	PDT	We saw increased cell death when HeLa cells were exposed to 630 nm light and cultured with nanocomposites^142
Gold nanospheres	808 nm at an output power of 32 W cm^−2 for 3 min	B16/F10 melanoma cells	PTT	NDP-MSH-PEG-HAuNS have the potential to mediate targeted photothermal ablation of melanoma^143	The internalisation and membrane wrapping of spherical particles have been extensively explored. Continuous wrapping, low adhesion energy, and low membrane energy barriers make spherical particles easier to absorb than nonspherical ones^144
Gold nanoshell	820 nm, 35 W cm^−2	Human breast carcinoma	PTT	When human breast cancer cells cultured with nanoshells were exposed to NIR light (820 nm, 35 W cm^−2), it was discovered that photothermally caused morbidity^145	Gold nanoshells (AuNSs) are nanoparticles with a gold coating on an inorganic (metal) or organic (polymer or lipid) core. Their unique features make them popular in medicine delivery. First, their resonance optical properties enable deep tissue penetration and rely on size and shape. They also absorb light and convert it into heat for photothermal ablation of cancer cells. AuNSs may release drugs at precise places when subjected to near-infrared (NIR) radiation. By functionalising these particles with ligands, they can connect to sick cell receptors for precise targeting. AuNSs are ideal for passive drug delivery because they accumulate in tumours via the enhanced permeability and retention (EPR) effect. Encasing nucleic acids, protecting them from degradation, and releasing them precisely by NIR irradiation, AuNSs may be employed in gene therapy^146
Gold nanoshell	670 nm (PDT) and λ = 810 nm	Head and neck carcinoma	PDT	In NIR irradiance, we observed significant cell inhibition at PDT radiant doses 80–100 times lower than those necessary for comparable outcomes with dual-function nanosystems^147
Gold nanoflower	808 nm (9 W cm^−2) for 5 minutes	HeLa cells	PTT	This kind of AuNF was shown to be non-toxic to HeLa cells when exposed to visible light, but NIR irradiation in vitro significantly increased photothermal ablation^148	Gold nanoflower has low toxicity to cells, and a strong photothermal effect^148
Gold nanoring	1064 nm, 200 mW	Oral cancer cells	PTT & PDT	By using the Au NP sample to compare the inactivation threshold intensities of NRI between fs and CW laser illuminations, we can see that fs laser illumination is more effective in cancer cell inactivation through the PTT effect when compared with CW laser illumination^149	Gold nanoring has a deeper tissue penetration^149

---

4.1 Gold nanoparticles for photothermal therapy

Due to its special qualities, gold nanoparticles have been a well-liked treatment agent for PTT.^110–112 In addition to their biocompatibility and low cytotoxicity, gold nanoparticles' easily modified surfaces and regulated physicochemical characteristics make them useful for various medicinal applications. PTT has profited from gold nanoparticles' adjustable absorption capabilities.^113,114

Because gold nanospheres readily produce heat when exposed to laser light at the wavelength of their surface plasmon resonance, they have been studied as PTT agents.¹¹⁵ For instance, 40 nm gold nanospheres were used to treat oral cancer cells in vitro using photothermal treatment.¹¹⁶ Gold nanostars measuring 30 nm were created by Liu et al. and demonstrated deep infiltration and high accumulation in malignancies.¹¹⁷ After 4 minutes of 980 nm laser irradiation at 50 °C, thermal ablation was caused by the superior photothermal action of gold nanostars. On the other hand, gold nanostars may melt and become nanospheres due to the heat generated by light.¹¹⁸ Consequently, it was proposed to use silica to modify the surface of gold nanostars to increase their photostability.¹¹⁹

Gold nanorods have two surface plasmon resonance peaks. The key element influencing the absorption characteristic of gold nanorods is their aspect ratio.¹²⁰ A multifunctional nanoparticle was developed by Yi et al.¹²¹ They created gold nanorods whose greatest absorption was measured at 670 nm, the excitation laser's wavelength. After four minutes of laser irradiation, the temperature rose to 45 °C, causing tissue injury. As a result, the interesting characteristics and unique capabilities of gold nanorods make them appropriate for PTT agents. Gold nanoparticles in PTT are shown in Fig. 6.

Fig. 6 Gold nanoparticles in PDT and PTT [a] schematic illustration of MMP-induced aggregation of AuNPs in vivo for enhanced PAI/PTT of tumor, reprinted with permission from ref. 134, Copyright 2019 Elsevier; and [b] illustration of the conjugation of a scintillator complex and gold nanorods for PTT/PDT synergic therapy of tumors. Reprinted with permission from ref. 135, Copyright 2020 American Chemical Society.

4.2 Gold nanoparticles for photodynamic therapy

PDT is a potential treatment for the management of malignant conditions like cancer if PS is selected carefully. It is usually characterized by a low rate of illness, excellent tolerability, minimally intrusive techniques, recurrent usage, minimum impairment, and often outpatient care.^122–124 Much research is being done to develop gold-containing nanocomposite PS with unique properties that may overcome some of the limitations of PDT applications and boost productivity to overcome the shortcomings of presently utilized PS Particularly in hydrophobic formulations, gold nanoparticles provide an excellent biocompatible PS carrier.^125–127 Furthermore, PS. molecules may be conjugated or encapsulated on the gold nanoparticle's surface. For example, gold nanoparticles were adsorbed with hypericin (Hyp) photosensitiser (PS) to increase the cellular absorption of hypericin in breast cancer.¹²⁸ In order to increase ZnPcS₄ bioavailability and phototoxicity in two and three-dimensional tumour models, the compound was encapsulated in AuNP and paired with targeted antibodies.¹²⁹ Every choice has benefits and drawbacks. Following light irradiation, the PS molecules on the NP surface might eventually cause tumor death by separating from the nanocarrier spontaneously or enzymatically and adhering to the prokaryotic membrane. The gold nanoparticle may interfere with PS's photoactivity, but PS within the NP is more protected from deterioration than PS at the surface from the environment of living things on route to the tumor.¹³⁰

According to many reports, when PS is combined with gold nanoparticles increases PS accumulation and ROS production, which is a key component of photodynamic treatment.¹³¹ When PEGylated gold nanoparticles were used in vivo instead of traditional PDT drug delivery, Pc4 administration increased by around two times. The only noticeable negative effect of the therapy in vivo was the presence of Pc4 throughout the whole body of the mouse, including the kidneys and lungs. Tumor necrosis and size decreased one week after PDT due to the therapeutic impact.¹³²

Researchers also examined the effectiveness of intravenously injecting mice with subcutaneously implanted murine melanoma (B78H1 cells) using C11Pc (phthalocyanine derivative)-conjugated AuNP. The AuNP–C11Pc combination was shown to aim for cancerous tissues more preferentially than the free C11Pc. Furthermore, it promoted an antiangiogenic reaction by severely damaging blood capillary and endothelial cells, generating a more widespread PDT response. On the other hand, the spleen and liver absorbed the AuNP–C11Pc compound, and it persisted in the liver for up to a week without seeming to lower PS.¹³³ Gold nanoparticles in PDT are shown in Fig. 6.

5. Application of gold nanoparticles in PTT and PDT

Gold nanoparticles' special qualities make them popular in various applications. Their multifunctionality, ability to deliver hydrophobic compounds, ability to actively and passively target disease cells, ability to extend the duration of a drug's circulation, and promotion of drug safety and tolerability are just a few of their advantages.¹⁵⁰

Scientists are interested in using gold nanoparticles as drug carriers due to their optical, tunable, and surface plasmon resonance (SPR) characteristics. Controlling their dispersion is simpler because of the wide variety of core diameters (1 to 150 nm) in which they may be manufactured. Gold nanoparticles are readily mutable because of their negative charge on their surface. This implies that adding other biomolecules, such as medications, targeting ligands, and genes, will make them readily functional. Furthermore, gold nanoparticles are a great option for usage as drug carriers due to their non-toxic nature and biocompatibility.^151,152 For instance, conjugating the long-used cancer treatment drug methotrexate (MTX) with gold nanoparticles increased the drug's cytotoxicity against a variety of tumor cell lines as compared to MTX administered alone. When coupled with gold nanoparticles, MTX accumulated in the tumor cells more quickly and to a greater degree.¹¹⁹

AuNPs are used in clinical diagnostics and other biological research due to their SPR, magnetic resonance, and fluorescence capabilities. The use of surface plasmon resonance (SPR) with AuNPs is effective in several applications, including DNA hybridization, antibody characterization, and protein conformational studies.^153,154 When measuring biological processes at the cellular and molecular levels using magnetic resonance imaging (MRI), AuNPs' magnetic resonance characteristics come in handy. Quantifying the molecular alterations linked to the beginning and progression of pathological conditions aids in the early diagnosis and prognosis of illnesses like cancer.

Because they effectively quench fluorescence and absorb SPR, AuNPs are integral to PDT and are used to treat cancer and certain skin diseases. PDT employs PS and a laser as light-sensitizing agents. Singlet oxygen and very active free radicals produced by PS trigger necrosis or death in tumor cells after they have been exposed to it.¹⁵⁵

Transfection agents have been created using AuNPs scaffolds for treating genetic diseases and cancer via gene therapy. AuNP-conjugated oligonucleotide complexes have been used as intracellular gene agents to regulate protein expression in cells.¹⁵⁶ The expression of luciferase has been inhibited by using RNA-conjugated gold nanoparticles.¹⁵⁷

AuNPs are effective sensors for various analytes and compounds, such as proteins and sugars. The sensors are made to detect AuNPs and their different features in mind.¹⁵⁸ AuNPs are used in vivo for CT imaging as well as cell imaging. Their primary reason for usage is that they substitute for CT devices that rely on X-rays. They are used because of their improved body tolerance, easier attachment to the moiety, and higher absorbent coefficient. Due to their compact size and high concentration, AuNP exhibits excellent X-ray attenuation. This makes using imaging to detect cancer simpler¹⁵⁹ NIR light is employed for deep tumor imaging because tissue absorption is relatively poor for light with wavelengths >650 and <2000 nm. During whole-body scans, NIR-active probes called AuNPs are used to image cancer cells in human bodies. Tumor imaging uses AuNPs as a contrast agent when coupled with anti-EGFR antibodies.^160,161 AuNP may be used as a screening test kit to determine whether an individual has the COVID-19 virus. The RNA from the sample has been analysed using the AuNP-based kit, which operates at the molecular level, and it contributes to reliable viral identification.¹⁶²

6. Clinical trial status of gold nanoparticles in cancer PDT and PTT

To accomplish the goal of oncotherapy in practical applications, particularly in clinical trials, it is often required to fully use the physical and chemical features of AuNPs. Table 3 lists the AuNPs currently being used in clinical studies.

Table 3 Summary of gold nanoparticles in clinical trials

ClinicalTrials.Gov identifier	Name	Application	Phase	Status
NCT03020017	Spherical nucleic acid (SNA) gold nanoparticle NU-0129: A	Glioblastoma gliosarcom	Early phase 1	Completed
NCT04907422	Gold nanoparticles	Carcinoma Ex pleomorphic adenoma of salivary glands	Observational	Completed
NCT07034248	Gold nanoparticle	Breast cancer	NA	Not yet recruiting
NCT06870994	Gold nanorod	Cutaneous metastatic melanoma	NA	Not yet recruiting
NCT00356980	Colloidal gold	Unspecified adult solid tumor	Phase 1	Completed

---

7. Challenges associated with gold nanoparticles for medication delivery systems

AuNP-assisted PTT and PDT seem promising, and it have shown encouraging benefits in cancer therapy. This approach can potentially be employed in cancer treatment and diagnosis. Several obstacles must be addressed before these therapies can be used in clinical settings. The use of gold nanoparticles in clinical practice is limited due to the lack of clinical studies that thoroughly investigate many parameters and markers. The start of clinical studies may broaden and clarify the uses of nanoparticles in medicine and diagnosis. However, they must be conducted after thorough safety and toxicity assessments of these nanoparticles.¹⁶³

Although there is a lot of interest in AuNPs, their therapeutic applications are limited by a few significant issues. Uncertainty about the toxicity profile of AuNPs in vivo is a major medical setback.¹⁶⁴ It could be difficult to minimize cytotoxicity while maintaining AuNPs' bioactivity and therapeutic qualities. Because of their low photothermal conversion efficiency, spherical AuNPs, for example, have limited promise despite their decreased toxicity.¹⁶⁵ However, according to different research, gold nanospheres and nanorods are more poisonous than other designs like flowers or stars. There is an urgent need for more varied and prolonged in vitro and in vivo research since the present in vivo data are inadequate and sometimes inconsistent.

As for potential accumulations, research has shown signs of sperm toxicity and residues of AuNPs in the heart, brain, and lungs, although as of yet, no long-term toxicity research has been conducted.¹⁶⁶ It's crucial to remember that current clinical studies for the treatment of various illnesses are brief and have tiny sample numbers, even if they haven't shown any significant harm. Therefore, to comprehend the possible impacts of gold buildup in different organs, bigger, longer-term research are required.¹⁶⁷ Fig. 7 shows the mechanisms of AuNP interaction with the immune system.

Fig. 7 Schematic overview of the mechanisms of AuNP interaction with the immune system. Reprinted with permission from ref. 168 under the terms and conditions of the Creative Commons Attribution (CC BY) license.

8. Future perspectives and conclusions

Nanomedicine's adaptable qualities might overcome even the most difficult limitations when used with photo-based treatment. By multifunctionalizing and delivering PS molecules to certain tissues, nanomedicine may provide cancer therapy a breakthrough over traditional treatment approaches.¹⁵⁹ Improving PDT and PTT specificity requires a critical step: clinical phases may use nanoparticles with enhanced physico-chemical characteristics. The delivery of PS is enhanced, and its solubility, circulation duration, and effectiveness are all increased when PS molecules are conjugated into NPs by active or passive targeting.^160,161

Gold nanoparticles are advantageous for biomedical applications because of their optical qualities and ease of synthesis, enabling simple conjugation with biological moieties. Crucially, the surface and core characteristics of gold nanoparticles may be tailored for single and many uses, such as chemical sensing, molecular recognition, and imaging. As a result, PDT and PTT are appealing methods for treating tumor cells. It is possible to inject millions of functionalized gold nanoparticles into the circulation, where they attach to certain cancer cells and either support PTT or PDT for effective tumor excision by surgery.

Even with these advancements in gold nanoparticle technology, more affordable gold nanoparticle-based solutions are still needed to provide highly precise early cancer detection and therapy. Understanding nanoparticles' characteristics and composition affecting their absorption and distribution throughout the body is the first step towards creating such a nanosystem.

A number of operational challenges, including rigid process parameters and a toxic microbial environment, have also been encountered in the microbial synthesis of AuNPs. Thus, in order to meet the increasing industrial demands for AuNPs, researchers are looking at cost-effective synthesis procedures due to the limitations of current techniques of synthesis.¹⁶⁹ The photosynthesis of AuNPs is acknowledged as an essential activity due to its renewable and ecologically beneficial characteristics. However, the effectiveness of synthetic processes is being impacted by the use of economically relevant plants and foods as stabilising and reducing agents. To improve the efficiency of the biosynthetic process, it is crucial to look into the reduction and stabilisation potential of non-commercially valued plants, especially biowastes, for the synthesis of AuNPs.¹⁷⁰

It is really interesting to precisely identify the bioactive compounds involved in the stabilization of AuNPs and the reduction of gold ions using both qualitative and quantitative approaches. That would be very helpful in creating AuNPs with the physiochemical properties that are needed for their possible uses. It would also demonstrate a greater comprehension of the actual reduction and stabilization process, as well as reaction synthesis, which has not yet been thoroughly investigated.

The synthesis circumstances significantly influence the physicochemical properties of biosynthesized AuNPs. Determining how process factors affect the dimensions and form of photosynthesized AuNPs is thus quite intriguing. In order to produce nanoparticles with the necessary dimensions and form—which will be very beneficial in selecting their appropriate prospective applications—it would be helpful to investigate the synthesis conditions on developing surface features of AuNPs. Since the size and form of nanoparticles have a significant impact on their future uses, the assessment of quantitative growth kinetics is very important. The growth kinetics of AuNPs produced using traditional techniques have been extensively reported in the literature. However, AuNP-mediated plant growth kinetics are still in the dark ages. Active nanoparticle targeting is theoretically also feasible, but more research is needed to figure out how to get past the immune system and reach the target. Therefore, it is essential to address several crucial aspects, including stability, long-term health impacts, repeatable and reliable production methods/assays, and cellular and immunological responses. This necessitates further study to refine the aforementioned strategies, especially in relation to PTT and active targeting. Furthermore, it is equally significant and vital to recognize it before using nanoparticle destiny in clinical trial applications. Therefore, more study in this area will be needed to address the ingestion of the nanoparticles, their subsequent location, any pertinent immune response, and, most crucially, their elimination from the human body.

Author contributions

A. A. Obalola: methodology, data curation, formal analysis, investigation, writing – original draft, visualization, software. H. Abrahamse: co-supervision, funding acquisition, resources. S. S. Dhilip Kumar: conceptualization, project administration, supervision, visualization, software, writing–review & editing, funding acquisition. All authors read and approved the final manuscript.

Conflicts of interest

The authors have declared no conflict of interest.

Data availability

No primary research results, software or code have been included and no new data were generated or analysed as part of this review.

Acknowledgements

This work is based on the research supported by the South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation of South Africa (Grant No. 98337), as well as grants received from the University of Johannesburg (URC), the National Research Foundation (NRF), and the CSIR (Council for Scientific and Industrial Research) – NLC (National Laser Centre) Laser Rental Pool Programme. The research reported in this publication was supported by the South African Medical Research Council under a Self-Initiated Research Grant. The views and opinions expressed are those of the author(s) and do not necessarily represent the official views of the SA MRC. The graphical abstract was created in BioRender. Dhilip kumar, S. (2025) https://biorender.com/sq11d9f.

References

1. WHO, Report On Cancer Setting Priorities, Investing Wisely And Providing Care For All 2020 WHO report on cancer: setting priorities, investing wisely and providing care for all, [Internet], 2020, Available from: http://apps.who.int/bookorders.
2. A. Sud, B. Kinnersley and R. S. Houlston, Genome-wide association studies of cancer: current insights and future perspectives, Nat. Rev. Cancer, 2017, 17(11), 692–704.
3. D. Cibula, R. Pötter, F. Planchamp, E. Avall-Lundqvist, D. Fischerova and C. Haie-Meder, et al., The European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology Guidelines for the Management of Patients with Cervical Cancer, Virchows Arch., 2018, 472(6), 919–936.
4. H. Tiwari, N. Rai, S. Singh, P. Gupta, A. Verma and A. K. Singh, et al., Recent Advances in Nanomaterials-Based Targeted Drug Delivery for Preclinical Cancer Diagnosis and Therapeutics, Bioengineering, 2023, 10(7), 760.
5. J. V. McGowan, R. Chung, A. Maulik, I. Piotrowska, J. M. Walker and D. M. Yellon, Anthracycline Chemotherapy and Cardiotoxicity, Cardiovasc. Drugs Ther., 2017, 31(1), 63–75.
6. S. Chen, R. Li, X. Li and J. Xie, Electrospinning: An enabling nanotechnology platform for drug delivery and regenerative medicine, Adv. Drug Delivery Rev., 2018, 132, 188–213.
7. S. Islam, M. M. S. Ahmed, M. A. Islam, N. Hossain and M. A. Chowdhury, Advances in nanoparticles in targeted drug delivery–A review, Results Surf. Interfaces, 2025, 100529.
8. W. Song, A. C. Anselmo and L. Huang, Nanotechnology intervention of the microbiome for cancer therapy, Nat. Nanotechnol., 2019, 14(12), 1093–1103.
9. M. K. Riaz, M. A. Riaz, X. Zhang, C. Lin, K. H. Wong and X. Chen, et al., Surface functionalization and targeting strategies of liposomes in solid tumor therapy: A review, Int. J. Mol. Sci., 2018, 19(1), 195.
10. Z. Wang, S. Gai, C. Wang, G. Yang, C. Zhong and Y. Dai, et al., Self-assembled zinc phthalocyanine nanoparticles as excellent photothermal/photodynamic synergistic agent for antitumor treatment, Chem. Eng. J., 2019, 361, 117–128.
11. H. Daraee, A. Eatemadi, E. Abbasi, S. F. Aval, M. Kouhi and A. Akbarzadeh, Application of gold nanoparticles in biomedical and drug delivery, Artif. Cells, Nanomed., Biotechnol., 2016, 44(1), 410–422.
12. A. Aghebati-Maleki, S. Dolati, M. Ahmadi, A. Baghbanzhadeh, M. Asadi and A. Fotouhi, et al., Nanoparticles and cancer therapy: Perspectives for application of nanoparticles in the treatment of cancers, J. Cell. Physiol., 2020, 235(3), 1962–1972.
13. H. Mishra, P. K. Mishra, A. Ekielski, M. Jaggi, Z. Iqbal and S. Talegaonkar, Melanoma treatment: from conventional to nanotechnology, J. Cancer Res. Clin. Oncol., 2018, 144(12), 2283–2302.
14. A. Alalmaie, H. T. Alshahrani, M. Alqahtani, Z. Alshahrani, S. Alahmari and A. Asiri, et al., Integrating computational insights in gold nanoparticle-mediated drug delivery: enhancing efficacy and precision, Front. Med. Technol., 2025, 7, 1528826.
15. L. Dykman, B. Khlebtsov and N. Khlebtsov, Drug delivery using gold nanoparticles, Adv. Drug Delivery Rev., 2025, 216, 115481.
16. Z. S. Dastgheib, S. S. Abolmaali, G. Farahavar, M. Salmanpour and A. M. Tamaddon, Gold nanostructures in melanoma: Advances in treatment, diagnosis, and theranostic applications, Heliyon, 2024, 10(15), e35655.
17. M. Zafar, M. Ijaz and T. Iqbal, Efficient Au nanostructures for NIR-responsive controlled drug delivery systems, Chem. Pap., 2021, 75(6), 2277–2293.
18. P. Singh and I. Mijakovic, Advances in gold nanoparticle technology as a tool for diagnostics and treatment of cancer, Expert Rev. Mol. Diagn., 2021, 21(7), 627–630.
19. I. Fratoddi, I. Venditti, C. Cametti and M. V. Russo, How toxic are gold nanoparticles? The state-of-the-art, Nano Res., 2015, 8(6), 1771–1799.
20. A. Hossain, M. T. Rayhan, M. H. Mobarak, M. I. H. Rimon, N. Hossain and S. Islam, et al., Advances and significances of gold nanoparticles in cancer treatment: A comprehensive review, Results Chem., 2024, 8, 101559.
21. T. H. Kim, M. Alle, S. C. Park, F. Zhao, W. Long and S. Samala, et al., Self-assembly prepared using an ion pair of poly(ethylene imine) and (phenylthio) acetic acid as a drug carrier for oxidation, temperature, and NIR-responsive release, Chem. Eng. J., 2021, 1, 415.
22. M. Alle, G. B. reddy, T. H. Kim, S. H. Park, S. H. Lee and J. C. Kim, Doxorubicin-carboxymethyl xanthan gum capped gold nanoparticles: Microwave synthesis, characterization, and anti-cancer activity, Carbohydr. Polym., 2020, 1, 229.
23. P. García Calavia, G. Bruce, L. Pérez-García and D. A. Russell, Photosensitiser-gold nanoparticle conjugates for photodynamic therapy of cancer, Photochem. Photobiol. Sci., 2018, 17(11), 1534–1552.
24. P. Agostinis, K. Berg, K. A. Cengel, T. H. Foster, A. W. Girotti, S. O. Gollnick, S. M. Hahn, M. R. Hamblin, A. Juzeniene, D. Kessel and M. Korbelik, Photodynamic therapy of cancer: An update, Ca-Cancer J. Clin., 2011, 61(4), 250–281.
25. D. C. Hone, P. I. Walker, R. Evans-Gowing, S. FitzGerald, A. Beeby and I. Chambrier, et al., Generation of cytotoxic singlet oxygen via phthalocyaninel-stabilized gold nanoparticles: A potential delivery vehicle for photodynamic therapy, Langmuir, 2002, 18(8), 2985–2987.
26. B. C. Wilson and R. A. Weersink, The Yin and Yang of PDT and PTT, Photochem. Photobiol., 2020, 96(2), 219–231.
27. X. Li, J. F. Lovell, J. Yoon and X. Chen, Clinical development and potential of photothermal and photodynamic therapies for cancer, Nat. Rev. Clin. Oncol., 2020, 17(11), 657–674.
28. T. Nunes, D. Hamdan, C. Leboeuf, M. El Bouchtaoui, G. Gapihan and T. T. Nguyen, et al., Targeting cancer stem cells to overcome chemoresistance, Int. J. Mol. Sci., 2018, 19(12), 4036.
29. H. C. Huang, I. Rizvi, J. Liu, S. Anbil, A. Kalra and H. Lee, et al., Photodynamic priming mitigates chemotherapeutic selection pressures and improves drug delivery, Cancer Res., 2018, 78(2), 558–571.
30. T. S. Hauck, T. L. Jennings, T. Yatsenko, J. C. Kumaradas and W. C. W. Chan, Enhancing the toxicity of cancer chemotherapeutics with gold nanorod hyperthermia, Adv. Mater., 2008, 20(20), 3832–3838.
31. M. Overchuk, K. M. Harmatys, S. Sindhwani, M. A. Rajora, A. Koebel and D. M. Charron, et al., Subtherapeutic Photodynamic Treatment Facilitates Tumor Nanomedicine Delivery and Overcomes Desmoplasia, Nano Lett., 2021, 21(1), 344–352.
32. V. Raeesi and W. Chan, Invitation for Special Issue on Cancer Nanomedicine Improving nanoparticle diffusion in a tumor collagen matrix by photo-thermal gold nanorods, Nanoscale, 2016, 8(25), 12524–12530.
33. B. Chen, B. W. Pogue, J. M. Luna, R. L. Hardman, P. J. Hoopes and T. Hasan, Tumor vascular permeabilization by vascular-targeting photosensitization: Effects, mechanism, and therapeutic implications, Clin. Cancer Res., 2006, 12(3 I), 917–923.
34. G. Shafirstein, D. Bellnier, E. Oakley, S. Hamilton, M. Potasek, K. Beeson and E. Parilov, Interstitial photodynamic therapy—a focused review, Cancers, 2017, 9(2), 12.
35. D. Gao, X. Guo, X. Zhang, S. Chen, Y. Wang, T. Chen, G. Huang, Y. Gao, Z. Tian and Z. J. Yang, Multifunctional phototheranostic nanomedicine for cancer imaging and treatment, Mater. Today Bio, 2020, 5, 100035.
36. F. Tang, A. Ding, Y. Xu, Y. Ye, L. Li, R. Xie and W. Huang, Gene and Photothermal Combination Therapy: Principle, Materials, and Amplified Anticancer Intervention, Small, 2024, 20(6), 2307078.
37. Y. Cai, T. Chai, W. Nguyen, J. Liu, E. Xiao, X. Ran, Y. Ran, D. Du, W. Chen and X. Chen, Phototherapy in cancer treatment: strategies and challenges, Signal Transduction Targeted Ther., 2025, 10(1), 115.
38. B. Nasseri, E. Alizadeh, F. Bani, S. Davaran, A. Akbarzadeh, N. Rabiee, A. Bahadori, M. Ziaei, M. Bagherzadeh, M. R. Saeb and M. Mozafari, Nanomaterials for photothermal and photodynamic cancer therapy, Appl. Phys. Rev., 2022, 9(1), 011317.
39. P. Y. Teo, W. Cheng, J. L. Hedrick and Y. Y. Yang, Co-delivery of drugs and plasmid DNA for cancer therapy, Adv. Drug Delivery Rev., 2016, 98, 41–63.
40. J. Shen, W. Zhang, R. Qi, Z. W. Mao and H. Shen, Engineering functional inorganic-organic hybrid systems: Advances in siRNA therapeutics, Chem. Soc. Rev., 2018, 47(6), 1969–1995.
41. S. Mehta, A. Suresh, Y. Nayak, R. Narayan and U. Y. Nayak, Hybrid nanostructures: Versatile systems for biomedical applications, Coord. Chem. Rev., 2022, 460, 214482.
42. Z. Ding, Y. Gu, C. Zheng, Y. Gu, J. Yang, D. Li, Y. Xu and P. Wang, Organic small molecule-based photothermal agents for cancer therapy: Design strategies from single-molecule optimization to synergistic enhancement, Coord. Chem. Rev., 2022, 464, 214564.
43. R. Ahuja, N. Panwar, J. Meena, M. Singh, D. P. Sarkar and A. K. Panda, Natural products and polymeric nanocarriers for cancer treatment: a review, Environ. Chem. Lett., 2020, 18(6), 2021–2030.
44. Z. Ding, Y. Gu, C. Zheng, Y. Gu, J. Yang, D. Li, Y. Xu and P. Wang, Organic small molecule-based photothermal agents for cancer therapy: Design strategies from single-molecule optimization to synergistic enhancement, Coord. Chem. Rev., 2022, 464, 214564.
45. M. M. Kim and A. Darafsheh, Light Sources and Dosimetry Techniques for Photodynamic Therapy, Photochem. Photobiol., 2020, 96(2), 280–294.
46. A. A. Obalola, H. Abrahamse and S. S. Dhilip Kumar, Enhanced therapeutic precision using dual drug-loaded nanomaterials for targeted cancer photodynamic therapy, Biomed. Pharmacother., 2025, 184, 117909.
47. M. M. Kim and A. Darafsheh, Light Sources and Dosimetry Techniques for Photodynamic Therapy, Photochem. Photobiol., 2020, 96(2), 280–294.
48. M. Overchuk, R. A. Weersink, B. C. Wilson and G. Zheng, Photodynamic and Photothermal Therapies: Synergy Opportunities for Nanomedicine, ACS Nano, 2023, 17(9), 7979–8003.
49. L. Fang, Z. Chen, J. Dai, Y. Pan, Y. Tu and Q. Meng, et al., Recent Advances in Strategies to Enhance Photodynamic and Photothermal Therapy Performance of Single-Component Organic Phototherapeutic Agents, Adv. Sci., 2025, 12(7), 2409157.
50. Y. Allamyradov, J. ben Yosef, B. Annamuradov, M. Ateyeh, C. Street and H. Whipple, et al., Photodynamic Therapy Review: Past, Present, Future, Opportunities and Challenges, Photochem, 2024, 4(4), 434–461.
51. F. L. Guern, T. S. Ouk, I. Yerzhan, Y. Nurlykyz, P. Arnoux and C. Frochot, et al., Photophysical and bactericidal properties of pyridinium and imidazolium porphyrins for photodynamic antimicrobial chemotherapy, Molecules, 2021, 26(4), 1122.
52. N. W. Nkune and H. Abrahamse, Nanoparticle-based drug delivery systems for photodynamic therapy of metastatic melanoma: A review, Int. J. Mol. Sci., 2021, 22(22), 12549.
53. J. Kadkhoda, A. Tarighatnia, J. Barar, A. Aghanejad and S. Davaran, Recent advances and trends in nanoparticles based photothermal and photodynamic therapy, Photodiagn. Photodyn. Ther., 2022, 37, 102697.
54. D. L. Sai, J. Lee, D. L. Nguyen and Y. P. Kim, Tailoring photosensitive ROS for advanced photodynamic therapy, Exp. Mol. Med., 2021, 53(4), 495–504.
55. A. Haleem, M. Javaid, R. P. Singh, S. Rab and R. Suman, Applications of nanotechnology in medical field: a brief review, Global Health J., 2023, 7(2), 70–77.
56. D. Suhag, A. Thakur and P. Thakur, Integrated Nanomaterials and Their Applications, Springer Nature, 2023, pp. 1–499.
57. S. Malik, K. Muhammad and Y. Waheed, Emerging Applications of Nanotechnology in Healthcare and Medicine, Molecules, 2023, 28(18), 6624.
58. M. C. Roco and W. S. Bainbridge, The new world of discovery, invention, and innovation: Convergence of knowledge, technology, and society, J. Nanopart. Res., 2013, 15(9), 1946.
59. M. Nikolova, R. Slavchov and G. Nikolova, Nanotechnology in Medicine, in Drug Discovery and Evaluation: Methods in Clinical Pharmacology, Springer International Publishing, 2nd edn, 2020, vol. 16, pp. 57–64.
60. D. Guo, G. Xie and J. Luo, Mechanical properties of nanoparticles: Basics and applications, J. Phys. D: Appl. Phys., 2013, 47(1), 013001.
61. T. Chen, L. Ren, X. Liu, M. Zhou, L. Li and J. Xu, et al., DNA nanotechnology for cancer diagnosis and therapy, Int. J. Mol. Sci., 2018, 19(6), 1671.
62. S. Song, Y. Qin, Y. He, Q. Huang, C. Fan and H. Y. Chen, Functional nanoprobes for ultrasensitive detection of biomolecules, Chem. Soc. Rev., 2010, 39(11), 4234–4243.
63. A. Gagliardi, E. Giuliano, E. Venkateswararao, M. Fresta, S. Bulotta, V. Awasthi and D. Cosco, Biodegradable Polymeric Nanoparticles for Drug Delivery to Solid Tumors, Front. Pharmacol., 2021, 12, 601626.
64. B. Kumar, S. Singh, I. Skvortsova and V. Kumar, Promising Targets in Anti-cancer Drug Development: Recent Updates, Curr. Med. Chem., 2017, 24(42), 4729–4752.
65. S. Siddique and J. C. L. Chow, Gold nanoparticles for drug delivery and cancer therapy, Appl. Sci., 2020, 10(11), 3824.
66. F. Abaszadeh, M. H. Ashoub, G. Khajouie and M. Amiri, Nanotechnology development in surgical applications: recent trends and developments, Eur. J. Med. Res., 2023, 28(1), 537.
67. N. Alrushaid, F. A. Khan, E. A. Al-Suhaimi and A. Elaissari, Nanotechnology in Cancer Diagnosis and Treatment, Pharmaceutics, 2023, 15(3), 1025.
68. B. Wang, S. Hu, Y. Teng, J. Chen, H. Wang and Y. Xu, et al., Current advance of nanotechnology in diagnosis and treatment for malignant tumors, Signal Transduction Targeted Ther., 2024, 9(1), 200.
69. X. Huang, P. K. Jain, I. H. El-Sayed and M. A. El-Sayed, Determination of the Minimum Temperature Required for Selective Photothermal Destruction of Cancer Cells with the Use of Immunotargeted Gold Nanoparticles, Photochem. Photobiol., 2006, 82(2), 412–417.
70. L. O. Svaasand, C. J. Gomer and E. Morinelli, On the Physical Rationale of Laser Induced Hyperthermia, Lasers Med. Sci., 1990, 5(2), 121–128.
71. A. R. Jain and M. Dhanraj, A clinical review of spacer design for conventional complete denture, Biol. Med., 2016, 8(5), 1.
72. J. Zhu, H. J. Lee, R. Huang, J. Zhou, J. Zhang, X. Yang, W. Zhou, W. Jiang and S. Chen, Harnessing nanotechnology for cancer treatment, Front. Bioeng. Biotechnol., 2025, 12, 1514890.
73. V. P. Zharov, E. N. Galitovskaya, C. Johnson and T. Kelly, Synergistic enhancement of selective nanophotothermolysis with gold nanoclusters: Potential for cancer therapy, Lasers Surg. Med., 2005, 37(3), 219–226.
74. V. Monge-Fuentes, L. A. Muehlmann and R. B. de Azevedo, Perspectives on the application of nanotechnology in photodynamic therapy for the treatment of melanoma, Nano Rev., 2014, 5(1), 24381.
75. S. Kwiatkowski, B. Knap, D. Przystupski, J. Saczko, E. Kędzierska, K. Knap-Czop, J. Kotlińska, O. Michel, K. Kotowski and J. Kulbacka, Photodynamic therapy – mechanisms, photosensitizers and combinations, Biomed. Pharmacother., 2018, 106, 1098–1107.
76. E. J. Hong, D. G. Choi and M. S. Shim, Targeted and effective photodynamic therapy for cancer using functionalized nanomaterials, Acta Pharm. Sin. B, 2016, 6(4), 297–307.
77. S. A. A. Rizvi and A. M. Saleh, Applications of nanoparticle systems in drug delivery technology, Saudi Pharm. J., 2018, 26(1), 64–70.
78. R. Soomro, M. Abdelmonem, B. A. Saputra and C. A. C. Abdullah, Enhancing oral cancer treatment via photodynamic therapy: Gold nanoparticle-based delivery system for 5-aminolevulinic acid (5-ALA), Oral Oncol. Rep., 2024, 11, 100642.
79. C. N. Honors, C. A. Kruger and H. Abrahamse, Photodynamic therapy for metastatic melanoma treatment: A review, Technol. Cancer Res. Treat., 2018, 17, 1533033818791795.
80. S. Aftab, A. Shah, A. Nadhman, S. Kurbanoglu, S. Aysıl Ozkan and D. D. Dionysiou, et al., Nanomedicine: An effective tool in cancer therapy, Int. J. Pharm., 2018, 540(1–2), 132–149.
81. T. Li, C. Guan, L. Xu, C. Li, Z. Song and N. Zhang, et al., Facile synthesis of MoS2@red phosphorus heterojunction for synergistically photodynamic and photothermal therapy of renal cell carcinoma, Colloids Surf., B, 2024, 241, 114031.
82. B. Bao, P. Su, K. Song, Y. Cui, X. Zhai and Y. Xu, et al., A Smart âSense-and-Treatâ Nanoplatform Based on Semiconducting Polymer Nanoparticles for Precise Photothermal-Photodynamic Combined Therapy, Biomacromolecules, 2021, 22(3), 1137–1146.
83. C. Zhang, J. Wu, W. Liu, X. Zheng and P. Wang, Natural-Origin Hypocrellin-HSA Assembly for Highly Efficient NIR Light-Responsive Phototheranostics against Hypoxic Tumors, ACS Appl. Mater. Interfaces, 2019, 11(48), 44989–44998.
84. Y. Liu, K. Yang, J. Wang, Y. Tian, B. Song and R. Zhang, Hypoxia-triggered degradable porphyrinic covalent organic framework for synergetic photodynamic and photothermal therapy of cancer, Mater. Today Bio, 2024, 25, 100981.
85. M. P. Romero, H. H. Buzza, M. D. Stringasci, B. M. Estevão, C. C. C. Silva and M. A. Pereira-Da-silva, et al., Graphene oxide theranostic effect: Conjugation of photothermal and photodynamic therapies based on an in vivo demonstration, Int. J. Nanomed., 2021, 16, 1601–1616.
86. S. Guo, Z. Song, D. K. Ji, G. Reina, J. D. Fauny and Y. Nishina, et al., Combined Photothermal and Photodynamic Therapy for Cancer Treatment Using a Multifunctional Graphene Oxide, Pharmaceutics, 2022, 14(7), 1365.
87. J. Peng, L. Zhao, X. Zhu, Y. Sun, W. Feng and Y. Gao, et al., Hollow silica nanoparticles loaded with hydrophobic phthalocyanine for near-infrared photodynamic and photothermal combination therapy, Biomaterials, 2013, 34(32), 7905–7912.
88. Z. X. Zhao, Y. Z. Huang, S. G. Shi, S. H. Tang, D. H. Li and X. L. Chen, Cancer therapy improvement with mesoporous silica nanoparticles combining photodynamic and photothermal therapy, Nanotechnology, 2014, 25(28), 285701.
89. X. Wei, H. Chen, H. P. Tham, N. Zhang, P. Xing and G. Zhang, et al., Combined photodynamic and photothermal therapy using cross-linked polyphosphazene nanospheres decorated with gold nanoparticles, ACS Appl. Nano Mater., 2018, 1(7), 3663–3672.
90. Z. Wang, S. Gai, C. Wang, G. Yang, C. Zhong and Y. Dai, et al., Self-assembled zinc phthalocyanine nanoparticles as excellent photothermal/photodynamic synergistic agent for antitumor treatment, Chem. Eng. J., 2019, 361, 117–128.
91. B. P. Jiang, L. F. Hu, X. C. Shen, S. C. Ji, Z. Shi and C. J. Liu, et al., One-step preparation of a water-soluble carbon nanohorn/phthalocyanine hybrid for dual-modality photothermal and photodynamic therapy, ACS Appl. Mater. Interfaces, 2014, 6(20), 18008–18017.
92. S. Bharathiraja, P. Manivasagan, M. Santha Moorthy, N. Q. Bui, B. Jang and T. T. V. Phan, et al., Photo-based PDT/PTT dual model killing and imaging of cancer cells using phycocyanin-polypyrrole nanoparticles, Eur. J. Pharm. Biopharm., 2018, 123, 20–30.
93. Y. Li, Z. Liu, Y. Hou, G. Yang, X. Fei and H. Zhao, et al., Multifunctional Nanoplatform Based on Black Phosphorus Quantum Dots for Bioimaging and Photodynamic/Photothermal Synergistic Cancer Therapy, ACS Appl. Mater. Interfaces, 2017, 9(30), 25098–25106.
94. A. Sahu, W. I. Choi, J. H. Lee and G. Tae, Graphene oxide mediated delivery of methylene blue for combined photodynamic and photothermal therapy, Biomaterials, 2013, 34(26), 6239–6248.
95. M. Ma, L. Cheng, A. Zhao, H. Zhang and A. Zhang, Pluronic-based graphene oxide-methylene blue nanocomposite for photodynamic/photothermal combined therapy of cancer cells, Photodiagn. Photodyn. Ther., 2020, 29, 101640.
96. P. Kalluru, R. Vankayala, C. S. Chiang and K. C. Hwang, Nano-graphene oxide-mediated In vivo fluorescence imaging and bimodal photodynamic and photothermal destruction of tumors, Biomaterials, 2016, 95, 1–10.
97. M. Zhang, W. Wang, Y. Cui, N. Zhou and J. Shen, Near-infrared light-mediated photodynamic/photothermal therapy nanoplatform by the assembly of Fe3O4 carbon dots with graphitic black phosphorus quantum dots, Int. J. Nanomed., 2018, 13, 2803–2819.
98. B. Acharya, A. Behera, S. Behera and S. Moharana, Recent Advances in Nanotechnology-Based Drug Delivery Systems for the Diagnosis and Treatment of Reproductive Disorders, ACS Appl. Bio Mater., 2024, 7(3), 1336–1361.
99. M. H. Akhter, M. Rizwanullah, J. Ahmad, M. J. Ahsan, M. A. Mujtaba and S. Amin, Nanocarriers in advanced drug targeting: setting novel paradigm in cancer therapeutics, Artif. Cells, Nanomed., Biotechnol., 2018, 46(5), 873–884.
100. J. Liao, Y. Jia, Y. Wu, K. Shi, D. Yang and P. Li, et al., Physical-, chemical-, and biological-responsive nanomedicine for cancer therapy, Wiley Interdiscip. Rev.:Nanomed. Nanobiotechnol., 2020, 12(1), e1581.
101. S. Hejmady, R. Pradhan, A. Alexander, M. Agrawal, G. Singhvi and B. Gorain, et al., Recent advances in targeted nanomedicine as promising antitumor therapeutics, Drug Discovery Today, 2020, 25(12), 2227–2244.
102. H. Zhang, S. Dong, Z. Li, X. Feng, W. Xu and C. M. S. Tulinao, et al., Biointerface engineering nanoplatforms for cancer-targeted drug delivery, Asian J. Pharm. Sci., 2020, 15(4), 397–415.
103. C. Jin, K. Wang, A. Oppong-Gyebi and J. Hu, Application of nanotechnology in cancer diagnosis and therapy - A mini-review, Int. J. Med. Sci., 2020, 17(18), 2964–2973.
104. A. Hedaoo, P. Khairnar, G. Vambhurkar, D. A. Srinivasarao, M. Negi and A. Shinde, et al., Unveiling the potential of inorganic nanoarchitecture-mediated photothermal therapy: An illustration on melanoma, Eur. Polym. J., 2024, 216, 113282.
105. R. Malekzadeh, T. Mortezazadeh, W. K. Abdulsahib, M. R. Hamblin, B. Mansoori, F. Alsaikhan and B. Zeng, Nanoarchitecture-based photothermal ablation of cancer: A systematic review, Environ. Res., 2023, 236, 116526.
106. X. Hai, M. Ji, K. Yu, T. Tian, Z. Cui, S. Bi and X. Zhang, Acid-responsive DNA-Au nanomachine with active/passive dual-targeting capacity for combinational cancer therapy, Mater. Today Nano, 2023, 23, 100355.
107. L. Liang, Y. Peng and L. Qiu, Mitochondria-targeted vitamin E succinate delivery for reversal of multidrug resistance, J. Controlled Release, 2021, 337, 117–131.
108. H. S. Kim and D. Y. Lee, Near-infrared-responsive cancer photothermal and photodynamic therapy using gold nanoparticles, Polymers, 2018, 10(9), 961.
109. H. Chen, L. Shao, T. Ming, Z. Sun, C. Zhao, B. Yang and J. Wang, Understanding the photothermal conversion efficiency of gold nanocrystals, Small, 2010, 6(20), 2272–2280.
110. M. A. Dheyab, A. A. Aziz, P. M. Khaniabadi, M. S. Jameel, N. Oladzadabbasabadi, A. A. Rahman, F. S. Braim and B. Mehrdel, Gold nanoparticles-based photothermal therapy for breast cancer, Photodiagn. Photodyn. Ther., 2023, 42, 103312.
111. T. Ferreira-Gonçalves, D. Nunes, E. Fortunato, R. Martins, A. P. de Almeida, L. Carvalho, D. Ferreira, J. Catarino, P. Faísca, H. A. Ferreira and M. M. Gaspar, Rational approach to design gold nanoparticles for photothermal therapy: the effect of gold salt on physicochemical, optical, and biological properties, Int. J. Pharm., 2024, 650, 123659.
112. M. N. Amaral, D. Nunes, E. Fortunato, R. Martins, C. Rodrigues, P. Faísca, H. A. Ferreira, J. M. Coelho, M. M. Gaspar and C. P. Reis, Gold nanoparticles for photothermal therapy – Influence of experimental conditions on the properties of resulting AuNPs, J. Drug Delivery Sci. Technol., 2024, 101, 106215.
113. F. Nouizi, M. Algarawi, H. Erkol and G. Gulsen, Gold nanoparticle-mediated photothermal therapy guidance with multi-wavelength photomagnetic imaging, Photodiagn. Photodyn. Ther., 2024, 45, 103956.
114. M. Broadbent, S. J. Chadwick, M. Brust and M. Volk, Gold Nanoparticles for Photothermal and Photodynamic Therapy, ACS Omega, 2024, 9(44), 44846–44859.
115. J. Choi, J. Yang, E. Jang, J. S. Suh, Y. M. Huh and K. H. S. Lee, Gold nanostructures as photothermal therapy agent for cancer, Anti-Cancer Agents Med. Chem., 2011, 11(10), 953–964.
116. I. H. El-Sayed, X. Huang and M. A. El-Sayed, Selective laser photo-thermal therapy of epithelial carcinoma using anti-EGFR antibody conjugated gold nanoparticles, Cancer Lett., 2006, 239(1), 129–135.
117. Y. Liu, J. R. Ashton, E. J. Moding, H. Yuan, J. K. Register and A. M. Fales, et al., A plasmonic gold nanostar theranostic probe for in vivo tumor imaging and photothermal therapy, Theranostics, 2015, 5(9), 946–960.
118. S. S. Chang, C. W. Shih, C. D. Chen, W. C. Lai and C. R. C. Wang, The Shape Transition of Gold Nanorods, Langmuir, 1999, 15(3), 701–709.
119. Y. Chen, C. Xu, Y. Cheng and Q. Cheng, Photostability enhancement of silica-coated gold nanostars for photoacoustic imaging guided photothermal therapy, Photoacoustics, 2021, 23, 100284.
120. S. Link and M. A. El-Sayed, Erratum: Simulation of the optical absorption spectra of gold nanorods as a function of their aspect ratio and the effect of the medium dielectric constant, J. Phys. Chem. B, 2005, 109(20), 10531–10532.
121. D. K. Yi, I. C. Sun, J. H. Ryu, H. Koo, C. W. Park and I. C. Youn, et al., Matrix metalloproteinase sensitive gold nanorod for simultaneous bioimaging and photothermal therapy of cancer, Bioconjugate Chem., 2010, 21(12), 2173–2177.
122. K. S. N. Turkmen, B. S. Rezaei, I. P. Aral, R. Shahbazi and K. Ulubayram, Gold nanoparticles-mediated photothermal and photodynamic therapies for cancer, Int. J. Pharm., 2024, 655, 124057.
123. Z. A. Lockwood, M. R. Jirousek, J. P. Basilion and C. Burda, Redefining cancer photodynamic therapy with gold nanoparticles, Photochem. Photobiol., 2025, 1120–1138.
124. O. Yeshchenko, P. Khort, O. Fedotov, V. Chumachenko, P. Virych and H. S. Warren, et al., Third-Generation Anticancer Photodynamic Therapy Systems Based on Star-like Anionic Polyacrylamide Polymer, Gold Nanoparticles, and Temoporfin Photosensitizer, Molecules, 2024, 29(10), 2224.
125. C. Liu, T. Tian, Y. Shi, M. Li, L. Hong, J. Zhou, J. Liu, Y. Zhong, X. Wang, Z. Wang and X. Bai, Enhancing antibacterial photodynamic therapy with NIR-activated gold nanoclusters: Atomic-precision size effect on reducing bacterial biofilm formation and virulence, Aggregate, 2025, 6(1), e666.
126. S. Ali, W. Hou, Z. Wang and Y. Song, Gold-Enhanced Lanthanide Nanomedicine for Near-Infrared Photodynamic Therapy, Langmuir, 2025, 41(29), 18965–18985.
127. D. Dehariya, A. Tarafdar, M. Pebam, S. A. Sankaranarayanan, S. Khatun and A. K. Rengan, Gold nanocages co-assembled with Spinacia oleracea extract combined photothermal/photodynamic therapy in 4T1 breast cancer cell line, Biomed. Mater., 2025, 20(2), 025014.
128. D. Mokoena, B. P. George and H. Abrahamse, Correction to: Conjugation of Hypericin to Gold Nanoparticles for Enhancement of Photodynamic Therapy in MCF-7 Breast Cancer Cells, Pharmaceutics, 2022, 14(10), 2212.
129. N. W. Nkune and H. Abrahamse, The phototoxic effect of a gold-antibody-based nanocarrier of phthalocyanine on melanoma monolayers and tumour spheroids, RSC Adv., 2024, 14(27), 19490–19504.
130. S. Wang, R. Gao, F. Zhou and M. Selke, Nanomaterials and singlet oxygen photosensitizers: Potential applications in photodynamic therapy, J. Mater. Chem., 2004, 14(4), 487–493.
131. H. P. Tham, H. Chen, Y. H. Tan, Q. Qu, S. Sreejith, L. Zhao, S. S. Venkatraman and Y. Zhao, Photosensitizer anchored gold nanorods for targeted combinational photothermal and photodynamic therapy, Chem. Commun., 2016, 52(57), 8854–8857.
132. S. Dixit, K. Miller, Y. Zhu, E. McKinnon, T. Novak, M. E. Kenney and A. M. Broome, Dual Receptor-Targeted Theranostic Nanoparticles for Localized Delivery and Activation of Photodynamic Therapy Drug in Glioblastomas, Mol. Pharm., 2015, 12(9), 3250–3260.
133. M. Camerin, M. Magaraggia, M. Soncin, G. Jori, M. Moreno, I. Chambrier, M. J. Cook and D. A. Russell, The in vivo efficacy of phthalocyanine-nanoparticle conjugates for the photodynamic therapy of amelanotic melanoma, Eur. J. Cancer, 2010, 46(10), 1910–1918.
134. K. Yang, Y. Liu, Y. Wang, Q. Ren, H. Guo, J. B. Matson, X. Chen and Z. Nie, Enzyme-induced in vivo assembly of gold nanoparticles for imaging-guided synergistic chemo-photothermal therapy of tumor, Biomaterials, 2019, 223, 119460.
135. L. Luo, W. Sun, Y. Feng, R. Qin, J. Zhang, D. Ding, T. Shi, X. Liu, X. Chen and H. Chen, Conjugation of a Scintillator Complex and Gold Nanorods for Dual-Modal Image-Guided Photothermal and X-ray-Induced Photodynamic Therapy of Tumors, ACS Appl. Mater. Interfaces, 2020, 12(11), 12591–12599.
136. L. Wu, B. Lin, H. Yang, J. Chen, Z. Mao, W. Wang and C. Gao, Enzyme-responsive multifunctional peptide coating of gold nanorods improves tumor targeting and photothermal therapy efficacy, Acta Biomater., 2019, 86, 363–372.
137. X. Tong, Z. Wang, X. Sun, J. Song, O. Jacobson and G. Niu, et al., Size dependent kinetics of gold nanorods in EPR mediated tumor delivery, Theranostics, 2016, 6(12), 2039–2051.
138. X. Yu, Z. Wang, H. Cui, X. Wu, W. Chai, J. Wei, Y. Chen and Z. Zhang, A Review on Gold Nanotriangles: Synthesis, Self-Assembly and Their Applications, Molecules, 2022, 27(24), 8766.
139. G. Terentyuk, E. Panfilova, V. Khanadeev, D. Chumakov, E. Genina, A. Bashkatov, V. Tuchin, A. Bucharskaya, G. Maslyakova, N. Khlebtsov and B. Khlebtsov, Gold nanorods with a hematoporphyrin-loaded silica shell for dual-modality photodynamic and photothermal treatment of tumors in vivo, Nano Res., 2014, 7(3), 325–337.
140. L. Au, D. Zheng, F. Zhou, Z. Y. Li, X. Li and Y. Xia, A quantitative study on the photothermal effect of immuno gold nanocages targeted to breast cancer cells, ACS Nano, 2008, 2(8), 1645–1652.
141. C. M. Cobley, L. Au, J. Chen and Y. Xia, Targeting gold nanocages to cancer cells for photothermal destruction and drug delivery, Expert Opin. Drug Delivery, 2010, 7(5), 577–587.
142. B. Khlebtsov, E. Panfilova, V. Khanadeev, O. Bibikova, G. Terentyuk, A. Ivanov, V. Rumyantseva, I. Shilov, A. Ryabova, V. Loshchenov and N. G. Khlebtsov, Nanocomposites containing silica-coated gold-silver nanocages and Yb-2,4-dimethoxyhematoporphyrin: Multifunctional capability of IR-luminescence detection, photosensitization, and photothermolysis, ACS Nano, 2011, 5(9), 7077–7089.
143. W. Lu, C. Xiong, G. Zhang, Q. Huang, R. Zhang, J. Z. Zhang and C. Li, Targeted photothermal ablation of murine melanomas with melanocyte-stimulating hormone analog - conjugated hollow gold nanospheres, Clin. Cancer Res., 2009, 15(3), 876–886.
144. S. Dasgupta, T. Auth and G. Gompper, Shape and orientation matter for the cellular uptake of nonspherical particles, Nano Lett., 2014, 14(2), 687–693.
145. L. R. Hirsch, R. J. Stafford, J. A. Bankson, S. R. Sershen, B. Rivera, R. E. Price, J. D. Hazle, N. J. Halas and J. L. West, Nanoshell-mediated near-infrared thermal therapy of tumors under magnetic resonance guidance, Proc. Natl. Acad. Sci. U. S. A., 2003, 100(23), 13549–13554.
146. B. Singhana, P. Slattery, A. Chen, M. Wallace and M. P. Melancon, Light-activatable gold nanoshells for drug delivery applications, AAPS PharmSciTech, 2014, 15(3), 741–752.
147. A. J. Trinidad, S. J. Hong, Q. Peng, S. J. Madsen and H. Hirschberg, Combined concurrent photodynamic and gold nanoshell-loaded macrophage-mediated photothermal therapies: An in vitro study on squamous cell head and neck carcinoma, Lasers Surg. Med., 2014, 46(4), 310–318.
148. J. Han, J. Li, W. Jia, L. Yao, X. Li and L. Jiang, et al., Photothermal therapy of cancer cells using novel hollow gold nanoflowers, Int. J. Nanomed., 2014, 9(1), 517–526.
149. C. K. Chu, Y. C. Tu, J. H. Hsiao, J. H. Yu, C. K. Yu, S. Y. Chen, P. H. Tseng, S. Chen, Y. W. Kiang and C. C. Yang, Combination of photothermal and photodynamic inactivation of cancer cells through surface plasmon resonance of a gold nanoring, Nanotechnology, 2016, 27(11), 115102.
150. E. Tan, P. Yin, X. Lang, X. Wang, T. You and L. Guo, Functionalized gold nanoparticles as nanosensor for sensitive and selective detection of silver ions and silver nanoparticles by surface-enhanced Raman scattering, Analyst, 2012, 137(17), 3925–3928.
151. G. Ajnai, A. Chiu, T. Kan, C. C. Cheng, T. H. Tsai and J. Chang, Trends of Gold Nanoparticle-based Drug Delivery System in Cancer Therapy, J. Exp. Clin. Med., 2014, 6(6), 172–178.
152. F. Y. Kong, J. W. Zhang, R. F. Li, Z. X. Wang, W. J. Wang and W. Wang, Unique roles of gold nanoparticles in drug delivery, targeting, and imaging applications, Molecules, 2017, 22(9), 1445.
153. J. Polte, Fundamental growth principles of colloidal metal nanoparticles - a new perspective, CrystEngComm, 2015, 17(36), 6809–6830.
154. Y. Wu, M. R. K. Ali, K. Chen, N. Fang and M. A. El-Sayed, Gold nanoparticles in biological optical imaging, Nano Today, 2019, 24, 120–140.
155. J. Narang, N. Malhotra, G. Singh and C. S. Pundir, Electrochemical impediometric detection of anti-HIV drug taking gold nanorods as a sensing interface, Biosens. Bioelectron., 2015, 66, 332–337.
156. N. L. Rosi, D. A. Giljohann, C. S. Thaxton, A. K. R. Lytton-Jean, M. S. Han and C. A. Mirkin, Oligonucleotide-modified gold nanoparticles for infracellular gene regulation, Science, 2006, 312(5776), 1027–1030.
157. D. A. Giljohann, D. S. Seferos, A. E. Prigodich, P. C. Patel and C. A. Mirkin, Gene regulation with polyvalent siRNA-nanoparticle conjugates, J. Am. Chem. Soc., 2009, 131(6), 2072–2073.
158. N. Elahi, M. Kamali and M. H. Baghersad, Recent biomedical applications of gold nanoparticles: A review, Talanta, 2018, 184, 537–556.
159. X. D. Zhang, H. Y. Wu, D. Wu, Y. Y. Wang, J. H. Chang, Z. B. Zhai, A. M. Meng, P. X. Liu, L. A. Zhang and F. Y. Fan, Toxicologic effects of gold nanoparticles in vivo by different administration routes, Int. J. Nanomed., 2010, 5, 771–781.
160. R. Sakthi Devi, A. Girigoswami, M. Siddharth and K. Girigoswami, Applications of Gold and Silver Nanoparticles in Theranostics, Appl. Biochem. Biotechnol., 2022, 194(9), 4187–4219.
161. K. Sokolov, M. Follen, J. Aaron, I. Pavlova, A. Malpica, R. Lotan and R. Richards-Kortum, Real-Time Vital Optical Imaging of Precancer Using Anti-Epidermal Growth Factor Receptor Antibodies Conjugated to Gold Nanoparticles, Cancer Res., 2003, 63(9), 1999–2004.
162. J. Wang, A. J. Drelich, C. M. Hopkins, S. Mecozzi, L. Li and G. Kwon, et al., Gold nanoparticles in virus detection: Recent advances and potential considerations for SARS-CoV-2 testing development, Wiley Interdiscip. Rev.: Nanomed. Nanobiotechnol., 2022, 14(1), e1754.
163. Q. Dai, N. Bertleff-Zieschang, J. A. Braunger, M. Björnmalm, C. Cortez-Jugo and F. Caruso, Particle Targeting in Complex Biological Media, Adv. Healthcare Mater., 2018, 7(1), 1700575.
164. A. Sani, C. Cao and D. Cui, Toxicity of gold nanoparticles (AuNPs): A review, Biochem. Biophys. Rep., 2021, 26, 100991.
165. P. T. Sujai, S. Shamjith, M. M. Joseph and K. K. Maiti, Elucidating Gold-MnO2Core-Shell Nanoenvelope for Real Time SERS-Guided Photothermal Therapy on Pancreatic Cancer Cells, ACS Appl. Bio Mater., 2021, 4(6), 4962–4972.
166. M. Souri, M. Soltani, F. Moradi Kashkooli, M. Kiani Shahvandi, M. Chiani, F. S. Shariati, M. R. Mehrabi and L. L. Munn, Towards principled design of cancer nanomedicine to accelerate clinical translation, Mater. Today Bio, 2022, 13, 100208.
167. L. Yao, D. Bojic and M. Liu, Applications and safety of gold nanoparticles as therapeutic devices in clinical trials, J. Pharm. Anal., 2023, 13(9), 960–967.
168. H. Huang, R. Liu, J. Yang, J. Dai, S. Fan and J. Pi, et al., Gold Nanoparticles: Construction for Drug Delivery and Application in Cancer Immunotherapy, Pharmaceutics, 2023, 15(7), 1868.
169. A. Rana, K. Yadav and S. Jagadevan, A comprehensive review on green synthesis of nature-inspired metal nanoparticles: Mechanism, application and toxicity, J. Cleaner Prod., 2020, 272, 122880.
170. P. Velusamy, G. V. Kumar, V. Jeyanthi, J. Das and R. Pachaiappan, Bio-inspired green nanoparticles: Synthesis, mechanism, and antibacterial application, Toxicol. Res., 2016, 32(2), 95–102.

---