Synergistic Photothermal Therapy Research Articles

Functionalized Organic–Inorganic Liposome Nanocomposites for the Effective Photo-Thermal Therapy of Breast Cancer

Organic–inorganic nanocomposites for photothermal therapy of cancers emerged as a promising strategy against malignant tumors. However, it is still a big challenge to develop a nanocomposite system that can maximize the synergistic photo-thermal therapy effect as well as preserve high stability for simultaneous delivery of the chemotherapeutic drugs and photo-thermal agents. Here, we have exploited an organic liposome containing inorganic core for co-loading the aggregates of bovine serum albumin (BSA), indocyanine green (ICG), and doxorubicin (DOX), abbreviated as BID-liposomal nanocomposites. The three kinds of substances were aggregated in the core of liposomal nanocomposites through hydrophobic and electrostatic interactions. In vitro characterization shows that BID-liposomal nanocomposites were spherical nanoparticles with size of 30–50 nm and good storage stability. Moreover, BID-Liposomal nanocomposites illustrate the strongest cytotoxicity among all the formulations against murine 4T1 tumor cells. In breast cancer-bearing mouse models, BID liposomes lead to significant improvements in tumor inhibition effects with no obvious toxicity. Therefore, the BID-liposomal nanoparticle is believed to be a promising strategy for chemo-photo-thermal therapy against cancers.

A pH-response chemotherapy synergistic photothermal therapy for tumor suppression and bone regeneration by mussel-inspired Mg implant.

Primary malignant bone tumors can be life-threatening. Surgical resection of tumor plus chemotherapy is the standard clinical treatment. However, postoperative recovery is hindered due to tumor recurrence caused by residual tumor cells and bone defect caused by resection of tumor tissue. Herein, a multifunctional mussel-inspired film was fabricated on Mg alloy, that is, an inner hydrothermal-treated layer, a middle layer of polydopamine, and an outer layer of doxorubicin. The modified Mg alloy showed excellent photothermal effect and thermal/pH-controlled release of doxorubicin. The synergistic effect of chemotherapy and photothermal therapy enabled the modified Mg alloy to kill bone tumor in vitro and inhibit tumor growth in nude mice. Moreover, because of the controlled release of Mg ions and biocompatibility of polydopamine, the modified Mg alloy supported extracellular matrix mineralization, alkaline phosphatase activity, and bone-related gene expression in C3H10T1/2. Bone implantation model in rats verified that the modified Mg showed excellent osteointegration. These findings prove that the use of mussel-inspired multifunction film on Mg alloy offers a promising strategy for the therapy of primary malignant bone tumor.

NIR II Luminescence Imaging for Sentinel Lymph Node and Enhanced Chemo-/Photothermal Therapy for Breast Cancer.

In this research, a NIR II luminescence imaging and enhanced chemo-/photothermal therapy system of CuS-DOX-Nd/FA NPs for breast cancer and lymph node tracing under single 808 nm irradiation is proposed. Nd-DTPA molecular cluster with the NIR II imaging effect as the carrier was designed to load the ultrasmall CuS nanoparticles and chemotherapeutic drug doxorubicin hydrochloride (DOX). The composite probe is used for tumor lesion imaging and tracking the breast cancer sentinel lymph nodes with simultaneous chemo-/photothermal therapy (PTT) for breast cancer under the single 808 nm laser. This designed probe not only has high permeability and retention (EPR) targeting effect but also can respond to the tumor microenvironment (TME), realizing more precise and efficient release of DOX at the cancer focus. At the same time, CuS as a drug carrier has a good photothermal therapy effect (photothermal conversion efficiency: 27.9%). The serialized released chemotherapy DOX and synergistic PTT effect can be used to the treat the in situ breast cancer land and simultaneously kill the metastasis cancer. The system made the combined molecular clusters Nd-DTPA achieve NIR II imaging of tumor lesions of breast cancer and lymph node to obtain the integration of diagnosis of the transferred disease for better prognosis. The feasibility of the system had obvious tumor growth inhibition effect with NIR II imaging guided is verified by a series of in vitro and in vivo experiments.

Folate receptor-targeting semiconducting polymer dots hybrid mesoporous silica nanoparticles against rheumatoid arthritis through synergistic photothermal therapy, photodynamic therapy, and chemotherapy

With ideal optical properties, semiconducting polymer quantum dots (SPs) have become a research focus in recent years; a considerable number of studies have been devoted to the application of SPs in non-invasive and biosafety phototherapy with near-infrared (NIR) lasers. Nevertheless, the relatively poor stability of SPs in vitro and in vivo remains problematic. PCPDTBT was chosen to synthesize photothermal therapy (PTT) and photodynamic therapy (PDT) dual-model SPs, considering its low band gap and desirable absorption in the NIR window. For the first time, cetrimonium bromide was used as a stabilizer to guarantee the in vitro stability of SPs, and as a template to prepare SP hybrid mesoporous silica nanoparticles (SMs) to achieve long-term stability in vivo. The mesoporous structure of SMs was used as a reservoir for the hypoxia-activated prodrug Tirapazamine (TPZ). SMs were decorated with polyethylene glycol-folic acid (SMPFs) to specifically target activated macrophages in rheumatoid arthritis (RA). Upon an 808 nm NIR irradiation, the SMPFs generate intracellular hyperthermia and excessive singlet oxygen. Local hypoxia caused by molecular oxygen consumption simultaneously activates the cytotoxicity of TPZ, which effectively kills activated macrophages and inhibits the progression of arthritis. This triple PTT-PDT-chemo synergistic treatment suggests that SMPFs realize the in vivo application of SPs and may be a potential nano-vehicle for RA therapy with negligible side-toxicity.

Synergistic photodynamic and photothermal therapy of BODIPY-conjugated hyaluronic acid nanoparticles

The combination of photodynamic therapy (PDT) and photothermal therapy (PTT) has emerged as a promising strategy for complete tumor ablation therapy. Herein, a boron dipyrromethene (BODIPY)-conjugated hyaluronic acid polymer that can self-assemble to form the nanoparticles (BODIPY-HA NPs) was prepared for combined cancer PDT and PTT. The fluorescence emission and reactive oxygen species (ROS) generation of BODIPY-HA NPs were inhibited because of the π-π stacking behavior of BODIPY, resulting in photothermal effect under 808 nm light irradiation. Upon the internalization by cancer cells, the BODIPY-HA NPs could disassemble into BODIPY-HA molecules, with the recovery of the fluorescence and ROS generation for PDT. Importantly, in vitro results confirmed that combined PTT and PDT have exhibited better anticancer effect than PTT alone upon 808 nm laser irradiation. These results showed that the self-assembled BODIPY-HA NPs may be a promising nanomedicine for synergistic cancer PDT and PTT.

Second Near-Infrared Light-Activatable Polymeric Nanoantagonist for Photothermal Immunometabolic Cancer Therapy.

Immunometabolic modulation offers new opportunities to treat cancers as it is highly associated with cancer progression and immunosuppressive microenvironment. However, traditional regimens using nonselective small-molecule immunomodulators lead to the off-target adverse effects and insufficient therapeutic outcomes. Herein a second near-infrared (NIR-II) photothermally activatable semiconducting polymeric nanoantagonist (ASPA) for synergistic photothermal immunometabolic therapy of cancer is reported. ASPA backbone is obtained by conjugating vipadenant, an antagonist to adenosine A2A receptor, onto NIR-II light-absorbing semiconducting polymer via an azo-based thermolabile linker. Under deep-penetrating NIR-II photoirradiation, ASPA induces tumor thermal ablation and subsequently immunogenic cell death, triggers the cleavage of thermolabile linker, and releases the antagonist to block the immunosuppressive adenosinergic pathway. Such a remotely controlled immunometabolic regulation potentiates cytotoxic T cell functions while suppresses regulatory T cell activities, leading to efficient primary tumor inhibition, pulmonary metastasis prevention, and long-term immunological memory. Thereby, this work provides a generic polymeric approach for precise spatiotemporal regulation of cancer immunometabolism.

Synergistic Photothermal and Chemical Therapy by Smart Dual‐Functional Graphdiyne Nanosheets for Treatment of Parkinson's Disease (Adv. Therap. 7/2021)

The development of precise medicine for Parkinson's disease is one of the urgencies for neurologists, however, there is still shortage of effective methods. In article 2100082, Han Zhang and co-works utilize a novel two-dimensional Graphdiyne-based delivery platform for disease treatment. These biocompatible nanosheets exhibit excellent photothermal conversion ability and superb BBB permeability upon NIR irradiation with recovery of neurons in midbrain.

Mixed‐Metal MOF‐Derived Hollow Porous Nanocomposite for Trimodality Imaging Guided Reactive Oxygen Species‐Augmented Synergistic Therapy

AbstractHere an excellent trimodality imaging‐guided synergistic photothermal therapy (PTT)/photodynamic therapy (PDT)/chemodynamic therapy (CDT) is proposed. To this end, a mixed‐metal Cu/Zn‐metal‐organic framework (MOF) is first assembled at room temperature on a nano‐scale. Interestingly, heating the MOF results in a Cu+/2+‐coexisting hollow porous structure. Subsequent heating treatment is used to integrate Mn2+ and MnO2 in the presence of manganese(II) acetylacetonate. The hollow composite achieves efficient loading of a photosensitizer, indocyanine green (ICG). Under laser irradiation, the aggregated ICG achieves photothermal imaging and PTT. Once released in the tumor site, ICG exhibits fluorescence imaging and PDT capacity. Cu+/Mn2+ ions perform Fenton‐like reaction with H2O2 to produce cytotoxic •OH for the enhanced CDT. Cu2+/MnO2 scavenge glutathione to improve the reactive oxygen species‐based therapy, while the formed Mn2+ ions enable “turn on” magnetic resonance imaging. Significantly, O2 is produced from the catalytic decomposition of endogenous H2O2 to improve ICG‐mediated PDT. Moreover, photothermal‐induced local hyperthermia accelerates •OH generation to enhance CDT. This synergistic drug‐free antitumor strategy realizes high treatment efficacy and low side effects on normal tissues. Thus, this mixed‐metal MOF is an efficient strategy to realize hollow structures for multi‐function integration to improve therapeutic capacity.

Temperature-Feedback Nanoplatform for NIR-II Penta-Modal Imaging-Guided Synergistic Photothermal Therapy and CAR-NK Immunotherapy of Lung Cancer.

In this study, to visually acquire all-round structural and functional information of lung cancer while performing synergistic photothermal therapy (PTT) and tumor-targeting immunotherapy, a theranostic nanoplatform that introduced upconversion nanoparticles (UCNPs) and IR-1048 dye into the lipid-aptamer nanostructrure (UCILA) is constructed. Interestingly, the IR-1048 dye grafted into the lipid bilayer can serve as the theranostic agent for photoacoustic imaging, optical coherence tomography angiography, photothermal imaging, and PTT in the second near infrared (NIR-II) window. In addition, loaded in the inner part of UCILA, UCNPs possess the superior luminescence property and high X-ray attenuation coefficient, which can act as contrast agents for computed tomography (CT) and thermo-sensitive up-conversion luminescence (UCL) imaging, enabling real-time tracking of metabolic activity of tumor and temperature-feedback PTT. Furthermore, under the complementary guidance of penta-modal imaging and an accurate monitoring of in situ temperature change during PTT, UCILA exhibits its excellent capability for ablating the lung tumor with minimal side effects. Meanwhile, synergistic CAR-NK immunotherapy is carried out specifically to eradicate any possible residual tumor cells after PTT. Therefore, the UCILA nanoplatform is demonstrated as a multifunctional theranostic agent for both penta-modal imaging and temperature-feedback PTT while conducting targeting immunotherapy of lung cancer.

Cancer cell membrane camouflaged iridium complexes functionalized black-titanium nanoparticles for hierarchical-targeted synergistic NIR-II photothermal and sonodynamic therapy

The diagnosis and treatment of cancer is one of the biggest medical challenges of the century. Despite significant improvements, there remains an urgent need for novel anticancer procedures. Among the most promising approaches, increasing attention has been devoted towards photothermal and sonodynamic therapy in which sensitizers are activated upon light/ultrasound radiation to generate a cytotoxic effect. While these methods have undoubtedly shown a high therapeutic success, these techniques are intrinsically limited. Herein, the functionalization of black-titanium nanoparticle with iridium complexes and cancer cell membranes in a nanoplatform for hierarchical targeted synergistic photothermal and sonodynamic cancer imaging and therapy is proposed. The particles showed to generate efficiently heat upon irradiation and catalytically form reactive oxygen species upon ultrasound radiation. The nanoparticle formulation demonstrated to selectively localize in the mitochondria as well as to preferentially accumulate in cancerous over non-cancerous cells as well as in the tumor inside a mouse model, presenting a hierarchical targeting strategy. Upon synergistic irradiation at 1064 nm and ultrasound radiation, the nanoparticles were able to act as an imaging agent and identify the tumor site with high spatial resolution as well as act as a therapeutic agent and completely eradicate a tumor inside a mouse model.

Synergistic Photothermal and Chemical Therapy by Smart Dual‐Functional Graphdiyne Nanosheets for Treatment of Parkinson's Disease

AbstractSuccessful treatment of Parkinson's disease (PD) is impeded by limited permeability of the blood brain barrier (BBB) which causes unsatisfactory drug accumulation in the central nervous system (CNS). In the present study, a novel 2D graphdiyne (GDY)‐based nanoplatform is utilized for the delivery of minocycline (MN), one drug candidate for PD treatment. These GDY nanosheets are prepared by sonication and exhibit excellent photothermal (PT) conversion ability (≈32%) without obvious toxicity in vitro. MN can be loaded onto GDY by π–π stacking (≈90%) and near infrared (NIR) irradiation is able to trigger the release of more than 30% of the payload. The BBB permeability of GDY is confirmed in both cellular and animal models. The behavioral defects of PD mice can be corrected after the PT and chemical synergistic treatment performed by GDY, with the dopaminergic neuron counting restored to normal level. Nanosheets‐mediated PT treatment exhibits comparable therapeutic effects to that of L‐DOPA, a commercialized PD drug. No obvious damage to major organs or circulation system is detected and physiological parameters remain stable during the behavioral study. This GDY‐based delivery system can serve as a promising platform for loading chemical drugs targeting neurodegenerative disorders.

One-for-all phototheranostics: Single component AIE dots as multi-modality theranostic agent for fluorescence-photoacoustic imaging-guided synergistic cancer therapy

Construction of single component theranostic agent with one-for-all features to concurrently afford both multi-modality imaging and therapy is an appealing yet significantly challenging task. Herein, a type of luminogens with aggregation-induced emission (AIE) characteristics are tactfully designed and facilely synthesized. These AIE luminogens (AIEgens) exhibit long emission wavelengths, good photostability, remarkable biocompatibility, good reactive oxygen species (ROS) generation performance and excellent photothermal conversion efficiency, which allow them to be powerfully utilized for in vitro and in vivo cancer phototheranostics. The results show that one of the AIEgens is capable of precisely diagnosing solid tumors of mice by means of combined near-infrared-I/II (NIR-I/II) fluorescence-photoacoustic imaging, meanwhile this AIEgen can activate photodynamic and photothermal synergistic therapy (PDT-PTT) upon laser irradiation, resulting in excellent tumor elimination efficacy with only once injection and irradiation. This study thus provides a versatile platform for practical cancer theranostics.

Antibacterial Activity of Porous Gold Nanocomposites via NIR Light-Triggered Photothermal and Photodynamic Effects.

Phototherapeutic approaches, including photothermal therapy (PTT) and photodynamic therapy (PDT), have become a promising strategy to combat microbial pathogens and tackle the crisis brought about by antibiotic-resistant strains. Herein, porous gold nanoparticles (AuPNs) were synthesized as photothermal agents and loaded with indocyanine green (ICG), a common photosensitizer for PDT, to fabricate a nanosystem presenting near-infrared (NIR) light-triggered synchronous PTT and PDT effects. The AuPNs can not only convert NIR light into heat with a high photothermal conversion efficiency (50.6-68.5%), but also provide a porous structure to facilely load ICG molecules. The adsorption of ICG onto AuPNs was mainly driven by electrostatic and hydrophobic interactions with the surfactant layer of AuPNs, and the aggregate state of ICG significantly enhanced its generation of reactive oxygen species. Moreover, taking advantage of its synergistic PTT and PDT effect, the hybrid nanocomposites displayed a remarkable antibacterial effect to the gram-positive pathogen Staphylococcus aureus (S. aureus) upon 808 nm laser irradiation.

Rough Carbon-Iron Oxide Nanohybrids for Near-Infrared-II Light-Responsive Synergistic Antibacterial Therapy.

Infections caused by multidrug resistant bacteria are still a serious threat to human health. It is of great significance to explore effective alternative antibacterial strategies. Herein, carbon-iron oxide nanohybrids with rough surfaces (RCF) are developed for NIR-II light-responsive synergistic antibacterial therapy. RCF with excellent photothermal property and peroxidase-like activity could realize synergistic photothermal therapy (PTT)/chemodynamic therapy (CDT) in the NIR-II biowindow with improved penetration depth and low power density. More importantly, RCF with rough surfaces shows increased bacterial adhesion, thereby benefiting both CDT and PTT through effective interaction between RCF and bacteria. In vitro antibacterial experiments demonstrate a broad-spectrum synergistic antibacterial effect of RCF against Gram-negative Escherichia coli (E. coli), Gram-positive Staphylococcus aureus (S. aureus), and methicillin-resistant Staphylococcus aureus (MRSA). In addition, satisfactory biocompatibility makes RCF a promising antibacterial agent. Notably, the synergistic antibacterial performances in vivo could be achieved employing the rat wound model with MRSA infection. The current study proposes a facile strategy to construct antibacterial agents for practical antibacterial applications by the rational design of both composition and morphology. RCF with low power density NIR-II light responsive synergistic activity holds great potential in the effective treatment of drug-resistant bacterial infections.

Targeting Hypoxic Tumors with Hybrid Nanobullets for Oxygen-Independent Synergistic Photothermal and Thermodynamic Therapy

HighlightsAn all-organic hybrid nanobullets labeled as ZPA@HA-ACVA-AZ NBs was developed for the “precise strike”of hypoxic tumors through an oxygen-independently synergistic PTT/TDT, possessing therapeutic advantages over traditional ROS-mediated cancer treatment.By feat of dual-targeting effect from surface-modified HA (targeting CD44 receptors) and AZ (targeting CA IX), the nanobullets accumulated at hypoxic tumors efficiently.The synergism of intelligent nanobullets could suppress the primary breast tumor growth and lung metastasis via CA IX inhibition by AZ and synergistic PTT/TDT.

Temperature-Sensitive Lipid-Coated Carbon Nanotubes for Synergistic Photothermal Therapy and Gene Therapy.

The combination of photothermal therapy (PTT) and gene therapy (GT) shows great potential to achieve synergistic anti-tumor activity. However, the lack of a controlled release of genes from carriers remains a severe hindrance. Herein, peptide lipid (PL) and sucrose laurate (SL) were used to coat single-walled carbon nanotubes (SCNTs) and multi-walled carbon nanotubes (MCNTs) to form bifunctional delivery systems (denoted SCNT-PS and MCNT-PS, respectively) with excellent temperature-sensitivity and photothermal performance. CNT/siRNA suppressed tumor growth by silencing survivin expression while exhibiting photothermal effects under near-infrared (NIR) light. SCNT-PS/siRNA showed very high anti-tumor activity, resulting in the complete inhibition of some tumors. It was highly efficient for systemic delivery to tumor sites and to facilitate siRNA release owing to the phase transition of the temperature-sensitive lipids, due to PL and SL coating. Thus, SCNT-PS/siRNA is a promising anti-tumor nanocarrier for combined PTT and GT.

Near-infrared photoactivated nanomedicines for photothermal synergistic cancer therapy

Cancer nanomedicines have provided promising treatment strategies for the regression of several types of cancer, although there still exists a need for significant advances to improve their therapeutic outcomes and reduce side effects. In this context, photothermal therapy (PTT) that uses near-infrared (NIR) photoirradiation of photothermal agents to generate heat for localized thermal damages has been established as a safe therapeutic modality. In addition to direct ablation of tumors, the heat generated during PTT process can achieve on-demand release of other therapeutic compounds, regulation of gene transcription and enzyme activity and enhancement of chemical reactions in tumor tissues, thereby resulting in photothermal synergistic cancer therapy with obviously improved benefits. In this review, we summarize the recent developments in NIR photoactivated nanomedicines for photothermal synergistic cancer therapy. We introduce the designing principles and the working mechanisms of nanoparticles upon NIR photoirradiation and their applications in photothermal synergistic chemotherapy, enzyme therapy, gene therapy, photodynamic therapy, chemodynamic therapy, thermodynamic therapy, immunotherapy and their multimodal therapies for cancer. Moreover, we discuss the existing challenges and further perspectives in this field.

Biodegradable FeWOx nanoparticles for CT/MR imaging-guided synergistic photothermal, photodynamic, and chemodynamic therapy.

The development of a simple and effective single constituent multifunctional nanotheranostic platform producing a multimodality diagnostic signal and curing effect is still a challenge. Herein, we synthesized simple and biodegradable FeWOx ternary oxide nanoparticles and modified their surface with RGD-PEG-NH2 (FeWOx-PEG-RGD NPs), whereby resulting NPs possessed a (T2/T1) switchable MRI/CT dual-modal imaging ability and synergistic photothermal therapy (PTT)/photodynamic therapy (PDT)/chemodynamic therapy (CDT) capacity. We showed that FeWOx-PEG-RGD NPs enabled tumor accumulation under a magnetic field drive and RGD-mediated tumor penetration and implemented PTT/PDT treatment under 980 nm laser irradiation. In an acidic tumor microenvironment (TME) with a high hydrogen peroxide (H2O2) expression, NPs degraded to release Fe3+ and Fe2+, triggering a Fenton reaction to generate ˙OH for CDT. The released Fe2+ led to T2/T1 signal conversion for tracing cancer therapy, while the high X-ray attenuation coefficient of W also made it a good CT contrast agent for guided therapy. Thus, the structurally simple FeWOx-PEG-RGD was capable of mediating (T2/T1-weighted) MR/CT two modal imaging-guided PTT/PDT/CDT synergic therapy with a high accuracy and superb anticancer efficiency. The simple, degradable, rapid-clearance, and multifunctional FeWOx-PEG-RGD NPs provide a novel, promising, and versatile nanotheranostic platform.

Near-infrared small molecule coupled with rigidness and flexibility for high-performance multimodal imaging-guided photodynamic and photothermal synergistic therapy.

Photodynamic therapy (PDT) synergized photothermal therapy (PTT) shows superior clinical application prospects than single PDT or PTT. On the other hand, multimodal imaging can delineate comprehensive information about the lesion site and thus help to improve therapy accuracy. However, integrating all these functions into one single molecule is challenging, let alone balancing and maximizing the efficacy of each function. Herein, a near-infrared (NIR) small molecule (ETTC) with an "acceptor-donor-acceptor" structure was designed and synthesized by coupling rigity and flexibility to simultaneously achieve NIR-II fluorescence imaging (NIR-II FLI), photoacoustic imaging, PTT and PDT. The efficacy of each functionality was well balanced and optimized (NIR-II quantum yield: 3.0%; reactive oxygen species generation: 3.2-fold higher than ICG; photothermal conversion efficiency: 52.8%), which may be attributed to the coupling of the rigid and flexible structures in ETTC to tactically manipulate the energy dissipation paths (non-radiative against radiative decay). As a proof-of-concept, under the effective guidance of local-tumor imaging by PA and whole-body imaging by NIR-II FL, complete tumor eradication was achieved via PDT and PTT combinational therapy. This work provides a novel perspective into conceiving and developing single molecule for efficient versatile biomedical applications.

Black SnO <sub>2−<i>x</i></sub> Based Nanotheranostic for Imaging-Guided Photodynamic/Photothermal Synergistic Therapy in the Second Near-Infrared Window

The shallow penetration depth of photothermal agents in the first near-infrared (NIR-I) window significantly limits their therapeutic efficiency. Multifunctional nanotheranostic agents in the second near-infrared (NIR-II) window have drawn extensive attention for their combined treatment of tumors. Here, for the first time, we created oxygen-deficient black SnO2−x with strong NIR (700–1200 nm) light absorption with NaBH4 reduction from white SnO2. Hyaluronic acid (HA) could selectively target cancer cells overexpressed CD44 protein. After modification with HA, the obtained nanotheranostic SnO2−x@SiO2-HA showed high dispersity in aqueous solution and excellent biocompatibility. SnO2−x@SiO2-HA was confirmed to simultaneously generate enough hyperthermia and reactive oxygen species with single NIR-II (1064 nm) light irradiation. Because HA is highly affined to CD44 protein, SnO2−x@SiO2-HA has specific uptake by overexpressed CD44 cells and can be accurately transferred to the tumor site. Furthermore, tumor growth was significantly inhibited following synergistic photodynamic therapy (PDT) and photothermal therapy (PTT) with targeted specificity under the guidance of thermal/photoacoustic (PA) dual-modal imaging using 1064 nm laser irradiation in vivo. Moreover, SnO2−x@SiO2-HA accelerated wound healing. This work prominently extends the therapeutic utilization of semiconductor nanomaterials by changing their nanostructures and demonstrates for the first time that SnO2−x based therapeutic agents can accelerate wound healing.