Gold nanotheranostics: future emblem of cancer nanomedicine.

Photothermal therapy (PTT) is successfully integrated with photodynamic therapy (PDT) to effectively improve the curative effect of cancer. The therapy nanoplatform is based on hollow Pd (H-Pd) nanospheres conjugated with Ce6 (Pd@Ce6). H-Pd nanospheres and Ce6 work as PTT and PDT agents, respectively. The H-Pd nanospheres with tunable surface plasmon resonance (SPR) properties effectively absorb light with near-infrared (NIR) emission and then convert the light to heat, selectively killing tumor cells. The experimental results show that H-Pd nanospheres with a size of 90 nm have the strongest absorbance and exhibit a high photothermal conversion efficiency (η) of 70%. Moreover, the absorption intensity and photothermal properties of H-Pd nanospheres do not show any decrease after 6 months of storage at room temperature, showing their excellent stability. Furthermore, after Ce6 is conjugated onto the surface of H-Pd nanospheres using polyethylenimine (PEI) as a linker, Pd@Ce6 not only exhibits the capabilities of photothermal conversion but also generates singlet oxygen (1O2), realizing the integration of PDT and PTT. In cell experiments, 86% of HeLa cells are killed after Pd@Ce6 is simultaneously irradiated with 660 and 808 nm lasers for 5 min with a power of 0.5 and 2 W cm-2, respectively. This successful combination of PTT with PDT to eradicate cancer provides a noninvasive and harmless way for cancer therapy.

Due to the plasmonic resonance of surface electrons, nanoparticles can absorb light and transform the energy to generate heat. This photothermal energy conversion can be used for photothermal hyperthermia therapy against cancer and microbial infections. When combined with photodynamic therapy, a synergistic efficacy enhancement has been achieved. It is also used to induce the release of anticancer and antimicrobial drugs and photosensitizers from nanoconjugates used as carriers and delivery agents. Several nanomaterials exhibit plasmonic resonance and are therefore used as agents for photothermal therapy. Gold nanoparticles are among the most widely used, particularly nanorods. Nanorods have two plasmonic resonance absorption bands. The longitudinal plasmonic resonance gives rise to an intense absorption band in the near-infrared region. In contrast, the transverse plasmonic resonance gives rise to a band of much lower intensity in the 300–400 nm region. Other nanostructures include iron oxide nanorods and carbon nanotubes. Porphysomes are liposome-like nanostructures generated when phospholipid-conjugated porphyrins self-assemble. They are used for fluorescence-guided photothermal therapy in combination with photodynamic therapy. Copper sulphide nanoparticles exhibit photothermal conversion and reactive oxygen generation and are, therefore, useful agents for the photodynamic–photothermal therapy combination. Photothermal therapy, like photodynamic therapy, is severely limited by the tissue penetration depth of light, with optimal performance in the near-infrared region located therapeutic window. It is also potentially confounded by the photothermal radiation bystander effect, albeit without conclusive evidence.

Cancer is among the leading causes of mortality and morbidity in the world. Metallic nanoparticles, especially gold nanoparticles (AuNPs) have emerged to be attractive systems to circumvent the associated adverse effects. By the virtue of their unique properties of tunable size, shape, composition, optical properties, biocompatibility, minimal toxicity, multivalency, fluorescence-luminescence property and surface plasmon resonance; AuNPs have the potential to be used as drug delivery systems. It is vital to ensure that the drug reaches the target site of action for selective kill of cancer cells without harm to healthy cells. These AuNPs can be easily functionalized with a wide array of ligands like peptides, oligonucleotides, polymers, carbohydrates for active targeting to ensure site specific delivery and reduced systemic effects. AuNPs have been in-vestigated as carriers for gene delivery, drug delivery with or without photothermal therapy, in diagnosis based on radiation or spectroscopy. They have emerged as attractive theranostic approach in the overall management of cancer with superior benefit to risk features. In this review, we have discussed synthesis of different AuNPs (nanorods, spherical nanoparticles, and hollow AuNPs), their functionalization strategies and their applications in biomedical domain. Various research studies and clinical trials on application of AuNPs in diagnosis and therapeutics are highlighted.

As one of the diseases with high morbidity and low cure rate in the world, cancer has always threatened the health of the public. However, due to the complexity, diversity and heterogeneity of the tumor, it is difficult to inhibit tumor recurrence and metastasis by relying on surgery, radiotherapy or chemotherapy. Photothermal therapy (PTT) is a cancer treatment by laser irradiation, which converts light energy into heat energy mediated by photothermal agents, and induces local tissue hyperthermia to treat cancer. And it has attracted widespread attention because of its non-specificity, high tumor ablation efficiency, and low toxic side effects on normal cells. However, the clinical transformation process of PTT is also severely limited by some disadvantages including the inconvenience of the delivery, distribution and metabolic process of the photothermal agent and the inaccurate and incomplete evaluation of the results of cancer treatment. The researchers have designed a variety of photothermal agents with multimodal imaging capabilities for cancer diagnosis and treatment. These imaging methods include thermal imaging (TI), photoacoustic (PA) imaging, photoluminescence (PL) imaging, magnetic resonance imaging (MRI), X-ray computed tomography (CT) imaging, and positron emission tomography (PET) imaging. And the imaging-guided cancer treatments have improved the accuracy of tumor visual treatments and greatly facilitated the clinical transformation of PTT. At present, the trend of cancer treatment development has gradually changed from monotherapy to combination therapy. Other therapies in combination with PTT include photodynamic therapy (PDT), chemotherapy, immunotherapy, radiotherapy (RT), sonodynamic therapy (SDT), and other PTT-related therapies. These combination therapies overcome tumor heterogeneity and complexity, reversing multidrug resistance, and reduce unnecessary side effects, and can more effectively achieve cancer diagnosis and treatment. This review summarizes the recent advances in multimodal imaging-guided PTT and multitherapies in combination with PTT for cancer diagnosis and treatment. For a single photothermal treatment, it is often difficult for researchers to effectively monitor the delivery, distribution, metabolism, and excretion of photothermal agents, and to accurately and dynamically track and evaluate the real-time therapeutic effects of tumors. Various strategies have been developed to solve the problems of single photothermal therapy. The new nano-platforms based on PTT-based multimodal imaging methods or therapies reviewed in this paper combine cancer diagnosis and treatment, and effectively overcome the shortcomings of single photothermal anti-tumor therapy, which is difficult to visualize tumors and lack of therapeutic efficiency to provide the development of new cancer diagnosis and treatment technologies new opportunities. Whether it is a single photothermal therapy or a combination of photothermal therapy and other methods, there is still a long way to go to study its therapeutic mechanism and further applications. The ultimate goal of these studies is to go to the clinic, cure the tumor, and benefit mankind. It is believed that with the rapid development of nanotechnology and nanomedicine, these problems will be gradually solved, and the photothermal anti-tumor combination therapy based on multimodal imaging will surely make new breakthroughs.

Photodynamic therapy (PDT) is a clinically approved and minimally invasive form of cancer treatment. However, due to hypoxia at the tumor site and phototoxicity to normal tissues, monotherapies using photosensitizers remain suboptimal. This study aimed to develop a highly selective controlled catalase-enhanced synergistic photodynamic and photothermal cancer therapy based on gold nanostars.Methods: Gold nanostars (GNS) with high thermal conversion efficiency were used as the core for photothermal therapy (PTT) and the shell consisted of the photosensitizer Ce6-loaded mesoporous silicon. The shell was modified with catalase (E), which catalyzes the conversion of hydrogen peroxide to oxygen at the tumor site, alleviating hypoxia and increasing the effect of the photodynamic treatment. Finally, a phospholipid derivative with c(RGDyK) was used as the targeting moiety and the nanoparticle-encapsulating material.Results: The nanoprobe exhibited good dispersion, high stability, and high photothermal conversion efficiency (~28%) for PTT as well as a photodynamic "on-off" effect on Ce6 encapsulated in mesoporous channels. The "release" of Ce6 was only triggered under photothermal stimulation in vivo. Due to its targeting ability, 72 h after injection of the probe, the tumor site in mice showed an observable CT response. The combined treatment using photothermal therapy (PTT) and catalase-enhanced photo-controlled PDT exerted a superior effect to PTT or PDT monotherapies.Conclusion: Our findings demonstrate that the use of this intelligent nanoprobe for CT-targeted image-guided treatment of tumors with integrated photothermal therapy (PTT) and catalase-enhanced controlled photodynamic therapy (PDT) may provide a novel approach for cancer theranostics.

Graphene quantum dots (GQDs) hold great promise for photodynamic and photothermal cancer therapies. Their unique properties, such as exceptional photoluminescence, photothermal conversion efficiency, and surface functionalization capabilities, make them attractive candidates for targeted cancer treatment. GQDs have a high photothermal conversion efficiency, meaning they can efficiently convert light energy into heat, leading to localized hyperthermia in tumors. By targeting the tumor site with laser irradiation, GQD-based nanosystems can induce selective cancer cell destruction while sparing healthy tissues. In photodynamic therapy, light-sensitive compounds known as photosensitizers are activated by light of specific wavelengths, generating reactive oxygen species that induce cancer cell death. GQD-based nanosystems can act as excellent photosensitizers due to their ability to absorb light across a broad spectrum; their nanoscale size allows for deeper tissue penetration, enhancing the therapeutic effect. The combination of photothermal and photodynamic therapies using GQDs holds immense potential in cancer treatment. By integrating GQDs into this combination therapy approach, researchers aim to achieve enhanced therapeutic efficacy through synergistic effects. However, biodistribution and biodegradation of GQDs within the body present a significant hurdle to overcome, as ensuring their effective delivery to the tumor site and stability during treatment is crucial for therapeutic efficacy. In addition, achieving precise targeting specificity of GQDs to cancer cells is a challenging task that requires further exploration. Moreover, improving the photothermal conversion efficiency of GQDs, controlling reactive oxygen species generation for photodynamic therapy, and evaluating their long-term biocompatibility are all areas that demand attention. Scalability and cost-effectiveness of GQD synthesis methods, as well as obtaining regulatory approval for clinical applications, are also hurdles that need to be addressed. Further exploration of GQDs in photothermal and photodynamic cancer therapies holds promise for advancements in targeted drug delivery, personalized medicine approaches, and the development of innovative combination therapies. The purpose of this review is to critically examine the current trends and advancements in the application of GQDs in photothermal and photodynamic cancer therapies, highlighting their potential benefits, advantages, and future perspectives as well as addressing the crucial challenges that need to be overcome for their practical application in targeted cancer therapy.

Tunable narrow-linewidth surface plasmon resonances of graphene-wrapped dielectric nanoparticles in the visible and near-infrared

Photosensitizer-loaded gold nanorods for near infrared photodynamic and photothermal cancer therapy

Gold nanorods with small dimensions demonstrate better cellular uptake and absorption efficiency. The ability to synthesize gold nanorods while maintaining a tunable high aspect ratio is challenging as it requires careful control of reaction conditions, often employing additional steps such as pH modification or the use of polymeric additives. We demonstrate a seedless approach for the synthesis of mini (width < 10 nm) gold nanorods with tunable longitudinal surface plasmon resonance from ∼700 nm to >1000 nm and aspect ratios ranging from ∼3 to ∼7 without the use of any polymeric additives or pH modification. A single mild reducing agent, hydroquinone, allowed for up to ∼98% reaction yield from a gold precursor. A mechanism for elongation is proposed based on partial silver decoupling from the reaction. Finally, the particles were coated with various capping agents to allow functionalization and conjugation of mTHPC drug molecules, which are used in photodynamic treatments, and cytotoxic CTAB was removed to increase their biocompatibility.

Colloidal metal nanocrystals with strong, stable, and tunable localized surface plasmon resonances (SPRs) can be useful in a corrosive environment for many applications including field-enhanced spectroscopies, plasmon-mediated catalysis, etc. Here, a new synthetic strategy is reported that enables the epitaxial growth of a homogeneously alloyed AuAg shell on Au nanorod seeds, circumventing the phase segregation of Au and Ag encountered in conventional synthesis. The resulting core-shell structured bimetallic nanorods (AuNR@AuAg) have well-mixed Au and Ag atoms in their shell without discernible domains. This degree of mixing allows AuNR@AuAg to combine the high stability of Au with the superior plasmonic activity of Ag, thus outperforming seemingly similar nanostructures with monometallic shells (e.g., Ag-coated Au NRs (AuNR@Ag) and Au-coated Au NRs (AuNR@Au)). AuNR@AuAg is comparable to AuNR@Ag in plasmonic activity, but that it is markedly more stable toward oxidative treatment. Specifically, AuNR@AuAg and AuNR@Ag exhibit similarly strong signals in surface-enhanced Raman spectroscopy that are some 30-fold higher than that of AuNR@Au. When incubated with a H(2)O(2) solution (0.5 m), the plasmonic activity of AuNR@Ag immediately and severely decayed, whereas AuNR@AuAg retained its activity intact. Moreover, the longitudinal SPR frequency of AuNR@AuAg can be tuned throughout the red wavelengths (≈620-690 nm) by controlling the thickness of the AuAg alloy shell. The synthetic strategy is versatile to fabricate AuAg alloyed shells on different shaped Au, with prospects for new possibilities in the synthesis and application of plasmonic nanocrystals.

Plasmonic nanostructures have been recently used in elevated temperature applications such as sensing of high-energy systems and localized heat generation for heat-assisted magnetic recording, thermophotovaltaics, and photothermal therapy. However, plasmonic nanostructures exposed to elevated temperature often experience permanent deformations, which could significantly degrade performance of the plasmonic devices. Therefore, understanding of thermal deformation of plasmonic nanostructures and its influence on the device performance is essential to the development of robust high-performance plasmonic devices. Here, we report thermal deformation of lithographic planar gold nanopatch and nanohole arrays and its influence on surface plasmon resonance sensing. The gold nanostructures are fabricated on a silicon substrate and on the end-face of an optical fiber using electron-beam lithography and focused-ion-beam lithography, respectively. The fabricated gold nanostructures are exposed to cyclic thermal loading in the range of 25 °C to 500 °C. Through experimental and numerical studies, we investigate (i) thermal deformation modes of the gold nanostructures, (ii) influence of the gold nanostructure geometry on the degree and mechanism of the thermal deformation, and (iii) influence of the thermal deformation on performance of surface plasmon resonance sensing. The obtained understanding from these studies is expected to help guide the development of robust high-performance plasmonic sensors for monitoring in elevated temperature environments. Although the current work is focused on gold nanostructures, it can be extended to provide useful insights on thermal deformation of refractory plasmonic nanostructures at extreme temperature.

Herein, we have developed a composite antibacterial hydrogel with photodynamic therapy (PDT) and photothermal therapy (PTT) antibacterial capabilities, triggered by white light and NIR light irradiation. A water-insoluble conjugated polymer (PDPP) with photothermal ability was prepared into nanoparticles by the nanoprecipitation method, and the cell-penetrating peptide TAT was grafted on the surface of the nanoparticles. Based on our previous work that developed a hybrid hydrogel with an enhanced PDT effect from polyisocyanide (PIC) hydrogel and cationic conjugated polythiophene (PMNT), PDPP nanoparticles (CPNs-TAT) with photothermal ability are introduced to realize the synergistic antibacterial effect of PDT and PTT. Using the PIC hydrogel to combine PIC and CPNs-TAT has the following advantages. First, the PIC hydrogel can regulate the aggregation state of PMNT, making it better dispersed and improving its capacity of reactive oxygen species (ROS) production. Second, CPNs-TAT can be uniformly dispersed in the PIC hybrid, thereby avoiding the toxicity caused by too high local concentration, achieving a uniform increase in system temperature, and enhancing the therapeutic effect of PTT. Third, the PIC hybrid has the synergistic treatment effect of PDT and PTT. The PIC hybrid intelligently regulates its antibacterial ability through white light and NIR light, which can be used in the white light and NIR light areas. When irradiated with white light and NIR light sequentially, synergistic PDT and PTT exhibit stronger antibacterial ability than PDT or PTT alone. The combination of two antibacterial methods realizes the dual-control antibacterial hydrogel of PDT and PTT and provides an antibacterial mode based on PIC hybrids. Therefore, the PIC hybrids are promising as an antibacterial excipient for clinical wounds.

Gold nanostructures (GNSts) have emerged as substitute for conventional contrast agents in imaging techniques and therapeutic probes due to their tunable surface plasmon resonance and optical properties in near-infrared region. Thus GNSts provide platform for the amalgamation of diagnosis and treatment (theranostics) into a single molecule for a more precise treatment. Hence, the article talks about the application of GNSts in imaging techniques and provide a holistic view on differently shaped GNSts in cancer theranostics. However, with promises GNSts also face various hurdles for their use as theranostic probe which are primarily associated with toxicity. Finally, the article attempts to discuss the challenges faced by GNSts and the way ahead that need to be traversed to place them in nanomedicine.

In this study, to enhance deep tissue penetration by near-infrared (NIR) light, a novel superparamagnetic iron oxide-enclosed hollow gold nanoshell (SPIO-HGNS) structure with tunable size and surface plasmon resonance (SPR) in the NIR range was designed and synthesized through a two-step template-enabled galvanic replacement reaction. Here, Ag-coated SPIO (SPIO-Ag) was prepared as a template with tunable outer diameters by way of adjusting the Ag content. SPIO-HGNS with variable hollow gold inner diameters can then be synthesized based on the determined outer diameter of the SPIO-Ag template through a galvanic replacement reaction between HAuCl3 and Ag coating on the SPIO surface. With incrementing amounts of Ag, three SPIO-HGNS structures were synthesized with comparable shell thicknesses around 6.7 nm and an average inner diameter of 38.7, 39.4, and 40.7 nm, respectively, evidenced by TEM and ICP results. The structure of SPIO-HGNS was confirmed by identifying Au111 lattice and the elemental mapping of Fe and Au using energy-dispersive X-ray spectroscopy. The ultraviolet–visible-NIR absorption spectra showed red-shifted SPR peaks (820, 855, and 945 nm) with the increasing inner diameters of SPIO-HGNS, which was also supported by an absorption cross-section simulation. The photothermal results showed that the three SPIO-HGNS structures, when exposed to ~ 30 s of 400 mW laser irradiation, exhibited photothermal temperature rises of 5.9, 4.6, and 2.9 ℃, respectively. This study explored the tuning of SPR properties in NIR-responsive magneto-plasmonic nanoparticles through a facile preparation procedure, paving the way for potential applications in photothermal therapies.Graphical abstractThe NIR-responsive magneto-plasmonic SPIO-HGNS nanostructures were developed with tunable SPR properties and strong photothermal conversion capacities.

Gold nanostructures are among the noble metal nanomaterials being intensely studied due to their good biocompatibility, tunable localized surface plasmon resonance (SPR), and ease of modification. These properties give gold nanostructures many potential chemical and biomedical applications. Herein, we demonstrate the critical role of oxygen activation during the decomposition of hydrogen peroxide (H2O2) in the presence of photoexcited gold nanorods (AuNRs) by using electron spin resonance (ESR) techniques. Upon SPR excitation, O2 is activated first, and the resulting reactive intermediates further activate H2O2 to produce •OH. The reactive intermediates exhibit singlet oxygen-like (1O2-like) reactivity, indicated by 1O2-specific oxidation reaction, quenching behaviors, and the lack of the typical 1O2 ESR signal. In addition, by using the antioxidant sodium ascorbate (NaA) as an example, we show that hydroxyl radicals from H2O2 activation can induce much stronger NaA oxidation than that in the absence of H2O2. These results may have significant biomedical implications. For example, as oxidative stress levels are known to influence tumorigenesis and cancer progression, the ability to control redox status inside tumor microenvironments using noble metal nanostructures may provide new strategies for regulating the metabolism of reactive oxygen species and new approaches for cancer treatment.