Tumor Theranostics Research Articles

Marriage of a Dual-Plasmonic Interface and Optical Microfiber for NIR-II Cancer Theranostics.

The use of light as a powerful tool for disease treatment has introduced a new era in tumor treatment and provided abundant opportunities for light-based tumor theranostics. This work reports a photothermal theranostic fiber integrating cancer detection and therapeutic functions. Its self-heating effect can be tuned at ultralow powers and used for self-heating detection and tumor ablation. The fiber, consisting of a dual-plasmonic nanointerface and an optical microfiber, can be used to distinguish cancer cells from normal cells, quantify cancer cells, perform hyperthermal ablation of cancer cells, and evaluate the ablation efficacy. Its cancer cell ablation rate reaches 89% in a single treatment. In vitro and in vivo studies reveal quick, deep-tissue photonic hyperthermia in the NIR-II window, which can markedly ablate tumors. The marriage of a dual-plasmonic nanointerface and an optical microfiber presents a novel paradigm in photothermal therapy, offering the potential to surmount the challenges posed by limited light penetration depth, nonspecific accumulation in normal tissues, and inadvertent damage in current methods. This work thus provides insight for the exploration of an integrated theranostic platform with simultaneous functions in cancer diagnostics, therapeutics, and postoperative monitoring for future practical applications.

Relief of tumor hypoxia using a nanoenzyme amplifies NIR-II photoacoustic-guided photothermal therapy.

Hypoxia is a critical tumor microenvironment (TME) component. It significantly impacts tumor growth and metastasis and is known to be a major obstacle for cancer therapy. Integrating hypoxia modulation with imaging-based monitoring represents a promising strategy that holds the potential for enhancing tumor theranostics. Herein, a kind of nanoenzyme Prussian blue (PB) is synthesized as a metal-organic framework (MOF) to load the second near-infrared (NIR-II) small molecule dye IR1061, which could catalyze hydrogen peroxide to produce oxygen and provide a photothermal conversion element for photoacoustic imaging (PAI) and photothermal therapy (PTT). To enhance stability and biocompatibility, silica was used as a coating for an integrated nanoplatform (SPI). SPI was found to relieve the hypoxic nature of the TME effectively, thus suppressing tumor cell migration and downregulating the expression of heat shock protein 70 (HSP70), both of which led to an amplified NIR-II PTT effect in vitro and in vivo, guided by the NIR-II PAI. Furthermore, label-free multi-spectral PAI permitted the real-time evaluation of SPI as a putative tumor treatment. A clinical histological analysis confirmed the amplified treatment effect. Hence, SPI combined with PAI could offer a new approach for tumor diagnosing, treating, and monitoring.

Bromine Substitution Improves the Photothermal Performance of π-Conjugated Phototheranostic Molecules.

NIR-II fluorescence imaging-guided photothermal therapy (PTT) has been widely investigated due to its great application potential in tumor theranostics. PTT is an effective and non-invasive tumor treatment method that can adapt to tumor hypoxia; nevertheless, simple and effective strategies are still desired to develop new materials with excellent PTT properties to meet clinical requirements. In this work, we developed a bromine-substitution strategy to enhance the PTT of A-D-A'-D-A π-conjugated molecules. The experimental results reveal that bromine substitution can notably enhance the absorptivity (ϵ) and photothermal conversion efficiency (PCE) of the π-conjugated molecules, resulting in the brominated molecules generating two times more heat (ϵ808 nm ×PCE) than their unsubstituted counterpart. We disclose that the enhanced photothermal properties of bromine-substituted π-conjugated molecules are a combined outcome of the heavy-atom effect, enhanced ICT effect, and more intense bromine-mediate intermolecular π-π stacking. Finally, the NIR-II tumor imaging capability and efficient PTT tumor ablation of the brominated π-conjugated materials demonstrate that bromine substitution is a promising strategy for developing future high-performance NIR-II imaging-guided PTT agents.

Advances in Magnetic Carbon Dots: A Theranostics Platform for Fluorescence/Magnetic Resonance Bimodal Imaging and Therapy for Tumors.

Theranostics technology that combines tumor diagnosis or monitoring with therapy is an important direction for the future development of tumor treatment. It takes advantage of efficiently observing tumor tissues, monitoring tumor treatment in real time, and significantly improving the cure efficiency. Magnetic carbon dots (CDs) are of wide interest as molecular imaging probes, drug carriers, photosensitizers, and radiosensitizers in the integration of tumor fluorescence/magnetic resonance bimodal diagnosis and treatment because of their small size, good optical stability, magnetic relaxation rate, and biocompatibility. This review first analyzes and compares the synthesis methods and physicochemical properties of magnetic CDs in recent years and then concludes their mechanism in tumor fluorescence/magnetic resonance bimodal imaging and therapy in details. Subsequently, the research progress of their application in tumor theranostics are summarized. Finally, the problems and challenges of magnetic CDs for development at this stage are prospected. This review provides new ideas for their controlled synthesis and application in efficient and precise therapy for tumors.

Multimodal Imaging-Guided Photoimmunotherapy of Pancreatic Cancer by Organosilica Nanomedicine.

Immune checkpoint blockade (ICB) treatments have contributed to substantial clinical progress. However, challenges persist, including inefficient drug delivery and penetration into deep tumor areas, inadequate response to ICB treatments, and potential risk of inflammation due to over-activation of immune cells and uncontrolled release of cytokines following immunotherapy. In response, this study, for the first time, presents a multimodal imaging-guided organosilica nanomedicine (DCCGP) for photoimmunotherapy of pancreatic cancer. The novel DCCGP nanoplatform integrates fluorescence, magnetic resonance, and real-time infrared photothermal imaging, thereby enhancing diagnostic precision and treatment efficacy for pancreatic cancer. In addition, the incorporated copper sulfide nanoparticles (CuS NPs) lead to improved tumor penetration and provide external regulation of immunotherapy via photothermal stimulation. The synergistic immunotherapy effect is realized through the photothermal behavior of CuS NPs, inducing immunogenic cell death and relieving the immunosuppressive tumor microenvironment. Coupling photothermal stimulation with αPD-L1-induced ICB, the platform amplifies the clearance efficiency of tumor cells, achieving an optimized synergistic photoimmunotherapy effect. This study offers a promising strategy for the clinical application of ICB-based combined immunotherapy and presents valuable insights for applications of organosilica in precise tumor immunotherapy and theranostics.

Conjugated Nanoparticles for Solid Tumor Theranostics: Unraveling the Interplay of Known and Unknown Factors.

Cancer diagnoses have been increasing worldwide, and solid tumors are among the leading contributors to patient mortality, creating an enormous burden on the global healthcare system. Cancer is responsible for around 10.3 million deaths worldwide. Solid tumors are one of the most prevalent cancers observed in recent times. On the other hand, early diagnosis is a significant challenge that could save a person's life. Treatment with existing methods has pitfalls that limit the successful elimination of the disorder. Though nanoparticle-based imaging and therapeutics have shown a significant impact in healthcare, current methodologies for solid tumor treatment are insufficient. There are multiple complications associated with the diagnosis and management of solid tumors as well. Recently, surface-conjugated nanoparticles such as lipid nanoparticles, metallic nanoparticles, and quantum dots have shown positive results in solid tumor diagnostics and therapeutics in preclinical models. Other nanotheranostic material platforms such as plasmonic theranostics, magnetotheranostics, hybrid nanotheranostics, and graphene theranostics have also been explored. These nanoparticle theranostics ensure the appropriate targeting of tumors along with selective delivery of cargos (both imaging and therapeutic probes) without affecting the surrounding healthy tissues. Though they have multiple applications, nanoparticles still possess numerous limitations that need to be addressed in order to be fully utilized in the clinic. In this review, we outline the importance of materials and design strategies used to engineer nanoparticles in the treatment and diagnosis of solid tumors and how effectively each method overcomes the drawbacks of the current techniques. We also highlight the gaps in each material platform and how design considerations can address their limitations in future research directions.

Ultrafast Subcellular Biolabeling and Bioresponsive Real-Time Monitoring for Targeting Cancer Theranostics.

Cell heterogeneity poses a formidable challenge for tumor theranostics, requiring high-resolution strategies for intercellular bioanalysis between single cells. Nanoelectrode-based electrochemical analysis has attracted much attention due to its advantages of label-free characteristics, relatively low cost, and ultra-high resolution for single-cell analysis. Here, we have designed and developed a subcellular biolabeling and bioresponsive real-time monitoring strategy for precise bioimaging-guided cancer diagnosis and theranostics. Our observations revealed the apparent intracellular migration of biosynthetic Au nanoclusters (Au NCs) at different subcellular locations, i.e., from the mitochondria to the mitochondrion-free region in the cytoplasm, which may be helpful for controlling over the biosynthesis of Au NCs. Considering the precise biolabeling advantage of the intracellular biosynthetic Au NCs for biomedical imaging of cancers, it is important to realize the biosynthetic Au NC-enabled precise control in real-time theranostics of cancer cells. Therefore, this work raises the possibility to achieve subcellular monitoring of H2O2 for targeting cancer theranostics, thereby providing a new way to explore the underlying mechanism and imaging-guided tumor theranostics.

A sequential dual-locked strategy with pH-responsive activation of photosensitizers and precise Cerenkov radiation delivery for cancer theranostics

Cerenkov radiation (CR)-induced therapy (CRIT) has emerged as a promising modality to overcome the limitation of light penetration in conventional photodynamic therapy (PDT). Nevertheless, achieving a balance between efficacy and safety of CRIT remains a significant challenge. Here, we propose a dual-locked strategy that sequentially delivers a pH-activatable photosensitizer, bovine serum albumin (BSA)-packed chlorin e6 (Ce6) and MnO2 nanodots (BCM), and 68Ga-labeled CD47-targeting C2 nanobody (68Ga-C2) for safe and effective CRIT in tumors. BCM serves as both a tumor microenvironment (TME) modulator and a pH-activatable photosensitizer, which exhibits minimal phototoxicity in normal tissues due to its quenched fluorescence and attenuated inter-system crossing (ISC) induced by MnO2 nanodots. Upon exposure to the acidic TME, BCM “unlocks” its bifunctionality, triggering a self-cascade catalysis reaction to supply O2 and cytotoxic HO·, while simultaneously depleting GSH. Cerenkov radiation from 68Ga-C2, subsequently delivered, illuminates the activated Ce6 molecules in BCM, inducing a burst generation of singlet oxygen, which is further enhanced by the pre-modulated TME. The acidic TME and tumor-targeting 68Ga-C2 provide two “keys” to ensure a selective reactive oxygen species (ROS) burst in the tumor sites while minimizing ROS generation in normal tissues. This pH-activatable CRIT induces DNA damage and mitochondrial dysfunction of tumor cells, effectively suppressing tumor growth with minimal side effects on CD47-expressing LS174T tumor models. This study highlights the potential of using pH-activatable photosensitizers in cancer therapy and provides a reference for future research in CR-induced tumor theranostics.

P02.19.A ASSESSMENT OF HEAT SHOCK PROTEIN HSP70 EXPRESSION IN THE GLIOBLASTOMA STEM-LIKE CELLS

Abstract BACKGROUND Glioblastoma multiforme (GBM) is a malignant brain tumor characterized by poor prognosis. The search of biomarkers for early diagnosis and as targets and for tumor theranostics due to the aggressiveness of the disease is urgently needed. One of the promising targets for therapy of brain tumors is 70 kDa heat shock protein (Hsp70), which has been found on the plasma membrane of various tumor cells (including GBM) but not on normal cells. GBM, like other types of tumors, has cellular heterogeneity. In particular, it contains tumor stem-like cells (TSLCs), which are considered analogues of healthy stem cells and are largely responsible for disease progression, recurrence and mediate resistance to ongoing therapy. In the present work, the histological sections of human GBM were analyzed to identify and quantify the colocalization of the heat shock protein Hsp70 with TSLC markers using the Opal Multiplex analysis system. MATERIAL AND METHODS Histological sections were prepared in accordance with the standard protocol using postoperative material from patients with newly diagnosed GBM (n=15). Zones of necrosis and living tissue were identified on tumor sections. Based on a phenotyping map using the Pathology Views™ fluorescence image analysis software, Hsp70 colocalization was quantified with Nestin and Sox2 in the areas of necrosis and viable tissue employing primary antibodies (anti-Hsp70, anti-Nestin and anti-Sox2). The preparations were stained using an Opal 3-Plex Manual Detection Kit according to the manufacturer's protocol. RESULTS The expression of Hsp70 and TSLC markers (Nestin and Sox2) was detected. The obtained quantitative data did not reveal significant differences in the distribution of cells expressing Hsp70 in the areas of necrosis and viable tissue (36 and 41%, respectively), which may indicate their uniform distribution in the tumor. Sufficiently high colocalization of Hsp70 with Nestin and Sox2 factors was detected mainly in the zone of viable tissue (57 and 30%, respectively). CONCLUSION Colocalization of Hsp70 with TSLC markers indicates the prospects for further studies of Hsp70, as well as its use for targeted therapy of malignant brain tumors.

Tumor microenvironment-mediated NIR-I-to-NIR-II transformation of Au self-assembly for theranostics.

The misdiagnosis of tumors due to insufficient penetration depth or signal interference and damage to normal tissues due to indiscriminate treatment are the biggest challenges in using photothermal agents for clinical translation. To overcome these limitations, a strategy of switching from the near-infrared (NIR)-I region to the NIR-II region was developed based on tumor microenvironment (TME)-mediated gold (Au) self-assembly. Using zeolitic imidazolate framework-8 (ZIF-8) metal-organic framework-coated gold nanorods (AuNRs@ZIF-8) as a model photothermal agent, we demonstrated that only a NIR-I photoacoustic imaging signal was observed in normal tissue because ZIF-8 could prevent the aggregation of AuNRs. However, when ZIF-8 dissociated in the TME, the AuNRs aggregated to activate NIR-II photoacoustic imaging and attenuate the NIR-I signal, thereby allowing an accurate diagnosis of tumors based on signal transformation. Notably, TME-activated NIR-II photothermal therapy could also inhibit tumor growth. Therefore, this TME-activated NIR-I-to-NIR-II switching strategy could improve the accuracy of deep-tumor diagnoses and avoid the injury caused by undifferentiated treatment. STATEMENT OF SIGNIFICANCE: Photothermal agents used for photoacoustic imaging and photothermal therapy have garnered great attention for tumor theranostics. However, always "turned on" near-infrared (NIR)-I laser (700-1000nm)-responsive photothermal agents face issues of penetration depth and damage to normal tissues. In contrast, tumor microenvironment-activated NIR-II "smart" photothermal agents exhibit deeper penetration depth and tumor selectivity. Therefore, a NIR-I-to-NIR-II switching strategy was developed based on tumor microenvironment-mediated Au self-assembly. This work provides a new strategy for developing tumor microenvironment-activated NIR-II smart photothermal agents.

Facile Synthesis of Basic Copper Carbonate Nanosheets for Photoacoustic Imaging-Guided Tumor Apoptosis and Ferroptosis and the Extension Exploration of the Synthesis Method.

Elimination of tumor cells using carbonate nanomaterials with tumor microenvironment-responsive capacity has been explored as an effective strategy. However, their therapeutic outcomes are always compromised by the relatively low intratumoral accumulation and limited synthesis method. Herein, a novel kind of basic copper carbonate nanosheets was designed and prepared using a green synthesis method for photoacoustic imaging-guided tumor apoptosis and ferroptosis therapy. These nanosheets were synthesized with the assistance of dopamine and ammonium bicarbonate (NH4HCO3) and the loading of glucose oxidase (GOx). NH4HCO3 could not only provide an alkaline environment for the polymerization of dopamine but also supply carbonates for the growth of nanosheets. The formed nanosheets displayed good acid and near-infrared light responsiveness. After intercellular uptake, they could be degraded to release Cu2+ and GOx, generating hydroxyl radicals through a Cu+-mediated Fenton-like reaction, consuming glucose, up-regulating H2O2 levels, and down-regulating GSH levels. Tumor elimination could be achieved by hydroxyl radical-induced apoptosis and ferroptosis. More amusingly, this synthesis method can be extended to several kinds of mono-element and multi-element carbonate nanomaterials (e.g., Fe, Mn, and Co), showing great potential for further tumor theranostics.

A pH/GSH/Glucose Responsive Nanozyme for Tumor Cascade Amplified Starvation and Chemodynamic Theranostics.

Nanozymes have brought enormous opportunities for disease theranostics. Here, a self-enhanced catalytic nanocrystal based on a bismuth-manganese core-shell nanoflower containing glucose oxide (GOx), termed BDS-GOx@MnOx, was designed for 4T1 tumor theranostics in vitro and in vivo. The BDS-GOx@MnOx nanozymes enable enhanced starvation treatment (ST) and chemotherapy (CDT) with high efficacy and exhibit sensitive tumor microenvironment (TME) responsive character for tumor therapy as well as for tumor-enhanced computer tomography (CT) and magnetic resonance (MR) diagnostic imaging. The characters and mechanism of the BDS-GOx@MnOx nanozymes have also been systematically studied and revealed.

Exceedingly Small Magnetic Iron Oxide Nanoparticles for T1 -Weighted Magnetic Resonance Imaging and Imaging-Guided Therapy of Tumors.

Magnetic iron oxide nanoparticles (MIONs) based T2 -weighted magnetic resonance imaging (MRI) contrast agents (CAs) are liver-specific with good biocompatibility, but have been withdrawn from the market and replaced with Eovist (Gd-EOB-DTPA) due to their inherent limitations (e.g., susceptibility to artifacts, high magnetic moment, dark signals, long processing time of T2 imaging, and long waiting time for patients after administration). Without the disadvantages of Gd-chelates and MIONs, the recently emerging exceedingly small MIONs (ES-MIONs) (<5nm) are promising T1 CAs for MRI. However, there are rare review articles focusing on ES-MIONs for T1 -weighted MRI. Herein, the recent progress of ES-MIONs, including synthesis methods (the current basic synthesis methods and improved methods), surface modifications (artificial polymers, natural polymers, zwitterions, and functional protein), T1 -MRI visual strategies (structural remodeling, reversible self-assemblies, metal ions doped, T1 /T2 dual imaging modes, and PET/MRI strategy), and imaging-guided cancer therapy (chemotherapy, gene therapy, ferroptosis therapy, photothermal therapy, photodymatic therapy, radiotherapy, immuotherapy, sonodynamic therapy, and multimode therapy), is summarized. The detailed description of synthesis methods and applications of ES-MIONs in this review is anticipated to attract extensive interest from researchers in different fields and promote their participation in the establishment of ES-MIONs based nanoplatforms for tumor theranostics.

Hairpin cascade circuits on programmable DNA-nucleated spherical nucleic acid for intracellular targeted microRNA imaging

DNA molecular probes have been increasingly used for biological imaging and tumor theranostics. In particular, live-cell imaging of low abundance microRNA (miRNA) with high accuracy and efficiency was extremely important for understanding functions and dynamics of miRNA. Herein, an easy-to-obtain DNA-nucleated spherical nucleic acid (DSNA) was constructed by one pair of hairpin probes “sticked” on self-assembled three-dimensional (3D) urchin-like DNA nanostructures (UDNs) to realize sensitive imaging of tumor-related miRNA in living cells. UDNs were prepared through four short single-stranded DNA by a simple “one-pot” annealing process that took only a few minutes. Moreover, sticking the reactants of hairpin probes on the UDNs not only sped up the reaction kinetic rate, but also improved the sensitivity and efficiency of miRNA-triggered hairpin cascade circuits. Compared with traditional AuNP-based spherical nucleic acid, the DSNA possessed superb biocompatibility and stability, excellent cell internalization capability and accessibility, which endowed them tremendous advantages for the monitoring of miRNA in living cells. Therefore, our developed strategy exhibited great potential in sensitive imaging of intracellular miRNA, offering a new avenue for early tumor diagnosis and related biomedical research.

Noble Metal Nanoparticles in Biomedical Thermoplasmonics

The unique properties of metal nanoparticles (NPs) resulting from their localized surface plasmon resonance have led to the emergence and rapid development of promising scientific areas. One of these areas is thermoplasmonics, which is based on the ability of such NPs to effectively transform optical radiation into heat. We discuss the optical properties of noble metal NPs, the main approaches to their synthesis, as well as the latest advances of thermoplasmonics in the field of biomedicine. The focus of this review is on photothermal diagnostics and therapy (theranostics) of various diseases. Note that, in addition to theranostics of tumors, the prospects for the use of plasmonic NPs in cardiology, ophthalmology, the fight against bacterial and viral infections, and other biomedical fields have been analyzed.

Engineered Liposomes in Interventional Theranostics of Solid Tumors.

Engineered liposomal nanoparticles have unique characteristics as cargo carriers in cancer care and therapeutics. Liposomal theranostics have shown significant progress in preclinical and clinical cancer models in the past few years. Liposomal hybrid systems have not only been approved by the FDA but have also reached the market level. Nanosized liposomes are clinically proven systems for delivering multiple therapeutic as well as imaging agents to the target sites in (i) cancer theranostics of solid tumors, (ii) image-guided therapeutics, and (iii) combination therapeutic applications. The choice of diagnostics and therapeutics can intervene in the theranostics property of the engineered system. However, integrating imaging and therapeutics probes within lipid self-assembly "liposome" may compromise their overall theranostics performance. On the other hand, liposomal systems suffer from their fragile nature, site-selective tumor targeting, specific biodistribution and premature leakage of loaded cargo molecules before reaching the target site. Various engineering approaches, viz., grafting, conjugation, encapsulations, etc., have been investigated to overcome the aforementioned issues. It has been studied that surface-engineered liposomes demonstrate better tumor selectivity and improved therapeutic activity and retention in cells/or solid tumors. It should be noted that several other parameters like reproducibility, stability, smooth circulation, toxicity of vital organs, patient compliance, etc. must be addressed before using liposomal theranostics agents in solid tumors or clinical models. Herein, we have reviewed the importance and challenges of liposomal medicines in targeted cancer theranostics with their preclinical and clinical progress and a translational overview.

Highly bright stable organic radicals encapsulated by amphiphilic polypeptide for efficient near-infrared phototheranostics

Stable organic radical molecules have received extensive attention due to their unique electronic structure and photophysical properties, and the highly fluorescent quantum efficiency has great appeal to bioimaging. However, still scarce reports on the application of them on the therapy of tumors, especially theranostics. Here, 3,6-dibromocarbazole modified tris (2,4,6-trichlorophenyl) methane radical (TB) has been synthesized with high NIR fluorescence quantum efficiency, and free radical nanoparticles (NPs) have been prepared using the precursor of the radical doping strategy. The free radical molecule TB and its precursor molecule HTB were mixed in proportion and encapsulated with an amphiphilic polypeptide (PEG-PAsp) to obtain the NPs. The 4% NPs can achieve a high fluorescence quantum efficiency (18.68%) in the NIR region. In addition, the NPs also have a good ability to produce reactive oxygen species (ROS) under either normoxia or hypoxia conditions, which makes it possible for photodynamic therapy (PDT). Interestingly, the NPs also show preferable photothermal ability (PCE = 42.39%) for photothermal therapy (PTT). Both in vitro and in vivo studies reveal that the as-prepared radical NPS show a NIR fluorescence imaging-guided synergistic PTT and type I/II PDT to tumors. It provides new strategies and new clues for the application of free radical molecules in the theranostics of tumors.

Sequential Diagnosis and Treatment for Colon Cancer via Derived Iridium and Indocyanine Green Hybrid Nanomicelles.

Indocyanine green (ICG) has been widely explored for the theranostics of tumors. However, ICG mainly accumulates in the liver, spleen, or kidney in addition to in tumors, causing inaccurate diagnoses and impaired therapeutic effects under NIR irradiation. Herein, a hybrid nanomicelle was constructed by integrating hypoxia-sensitive iridium(III) and ICG for precise tumor localization and photothermal therapy in sequence. In this nanomicelle, the amphiphilic iridium(III) complex (BTPH)2Ir(SA-PEG) was synthesized through the coordination substitution of hydrophobic (BTPH)2IrCl2 and hydrophilic PEGlyated succinylacetone (SA-PEG). Meanwhile, PEGlyated ICG (ICG-PEG) as a derivative of the photosensitizer ICG was also synthesized. (BTPH)2Ir(SA-PEG) and ICG-PEG were coassembled by dialysis to form the hybrid nanomicelle M-Ir-ICG. Hypoxia-sensitive fluorescence, ROS generation, and the photothermal effect of M-Ir-ICG were investigated in vitro and in vivo. The experimental results indicated that M-Ir-ICG nanomicelles could locate at the tumor site first and then perform photothermal therapy with 83.90% TIR, demonstrating great potential for clinical applications.

NOBLE METAL NANOPARTICLES IN BIOMEDICAL THERMOPLASMONICS

The unique properties of metal nanoparticles (NPs) resulting from their localized surface plasmon resonance have led to the emergence and rapid development of promising scientific areas. One of these area is thermoplasmonics, which is based on the ability of such NPs to effectively transform optical radiation into heat. We discuss the optical properties of noble metal NPs, the main approaches to their synthesis, as well as the latest advances of thermoplasmonics in the field of biomedicine. The focus of this review is on photothermal diagnostics and therapy (theranostics) of various diseases. Note that, in addition to theranostics of tumors, the prospects for the use of plasmonic NPs in cardiology, ophthalmology, the fight against bacterial and viral infections, and other biomedical fields have been analyzed.

An ultrasound-activatable platinum prodrug for sono-sensitized chemotherapy

Despite the great success achieved by photoactivated chemotherapy, eradicating deep tumors using external sources with high tissue penetration depth remains a challenge. Here, we present cyaninplatin, a paradigm of Pt(IV) anticancer prodrug that can be activated by ultrasound in a precise and spatiotemporally controllable manner. Upon sono-activation, mitochondria-accumulated cyaninplatin exhibits strengthened mitochondrial DNA damage and cell killing efficiency, and the prodrug overcomes drug resistance as a consequence of combined effects from released Pt(II) chemotherapeutics, the depletion of intracellular reductants, and the burst of reactive oxygen species, which gives rise to a therapeutic approach, namely sono-sensitized chemotherapy (SSCT). Guided by high-resolution ultrasound, optical, and photoacoustic imaging modalities, cyaninplatin realizes the overall theranostics of tumors in vivo with superior efficacy and biosafety. This work highlights the practical utility of ultrasound to precisely activate Pt(IV) anticancer prodrugs for the eradication of deep tumor lesions and broadens the biomedical uses of Pt coordination complexes.