Copper Sulfide Nanoparticle-Redirected Macrophages for Adoptive Transfer Therapy of Melanoma

Adoptive cell therapy (ACT) has achieved landmark advances in treating cancer in clinic. Recent advances in ACT of macrophages engineered to express chimeric antigen receptors (CARs) have shown effectiveness in treating solid tumors. However, the CAR-macrophage therapy is dependent on tumor antigen recognition and gene editing methods. Herein, an adoptive macrophage therapy is presented through copper sulfide nanoparticle-regulation that exhibits substantial antitumor effect in melanoma-bearing mice, without the need for tumor antigen repertoire. Bone marrow derived macrophages (BMDMs) incubated with the nanoparticles promote the cellular production of reactive oxygen species (ROS) through dynamin-related protein 1 (Drp1)-mediated mitochodrial fission. The high intracellular ROS level directs BMDMs polarization toward M1 phenotype by classical IKK-dependent NF-κB activation. Moreover, the copper sulfide nanoparticle-stimulated BMDMs (CuS-MΦ) reduce the expression of programmed death-1 (PD-1) and exhibit enhanced phagocytic and digestive ability. Intratumoral transfer of CuS-MΦ significantly prolongs the median survival time of the tumor-bearing mice, remodels the tumor microenvironment, and elicits systemic antitumor immunity. These results suggest a cancer therapeutic approach of adoptively transferred macrophages through the induction of intracellular ROS with nanomaterials.     

Immunotherapeutic Hydrogel with Photothermal Induced Immunogenic Cell Death and STING Activation for Post-Surgical Treatment

Post-surgical tumor recurrence remains a major clinical concern for patients with malignant solid tumors. Herein, an immunotherapeutic hydrogel (SA_PBA/ZMC/ICG) is developed by incorporating metal ion-cyclic dinucleotide (CDN) nanoparticles (Zn-Mn-CDN, ZMC) and a photosensitizer (indocyanine green, ICG) into phenylboronic acid (PBA)-conjugated sodium alginate (SA_PBA) for photothermal therapy (PTT)-triggered in situ vaccination to inhibit post-surgical recurrence and metastasis of malignant tumors. The gelation of SA_PBA/ZMC/ICG in the residual tumors can achieve accurate local PTT and the local sustained release of CDN and Mn²⁺ with minimal detrimental off-target toxic effects. Furthermore, CDN, which is an agonist of the stimulator of interferon genes (STING), along with Mn²⁺ can activate the STING pathway and trigger type-I-IFN-driven immune responses against tumors. Therefore, the immunotherapeutic hydrogel with enhanced immune response by STING agonist and PTT-induced immunogenic cell death (ICD) reprograms the post-surgical immunosuppressive microenvironment, substantially decreasing the post-surgical recurrence and metastasis of solid tumors in multiple murine tumor models when administered during surgical resection. Taken together, PTT-triggered and STING-mediated in situ cancer vaccination is an effective therapeutic intervention for post-surgical recurrence and metastasis of tumors.     

Selenoprotein-Regulated Hydrogel for Ultrasound-Controlled Microenvironment Remodeling to Promote Bone Defect Repair

Abnormal levels of reactive oxygen species (ROS) and the hypoxic microenvironment within bone defects are important factors that impede bone repair processes. Herein, an innovative ultrasound-modulatable hydrogel platform with selenoprotein-mediated antioxidant effects to promote bone injury repair is presented. This hydrogel platform encapsulates oxygen-enriched selene-incorporated thin-shell silicon within methacrylate gelatin (O₂-PSSG). The resultant construct orchestrates the modulation of the bone-defect microenvironment, thereby expediting the course of bone regeneration. Ultrasound (US) is used to regulate the pore size of the hydrogel to release selenium-containing nanoparticles and promote the in situ synthesis of efficient intracellular selenoproteins and hydrogen peroxide consumption. As expected, O₂-PSSG rapidly releases selenocystine ([Sec]₂) under US control to scavenge reactive oxygen species and maintain the homeostasis of bone marrow mesenchymal stem cells (BMSCs). Over time, the action of the system by selenoprotein increases the activation of Wnt/β-catenin pathways and promotes the differentiation of BMSCs. Consequently, O₂-PSSG potentiates the antioxidant proficiency of BMSCs both in vitro and in vivo, alleviates hypoxic environments, promotes osteogenic differentiation, and expedites cranial bone repair in rat models. In summary, this study suggests that the designed and constructed US-responsive antioxidant hydrogel is a promising prospective strategy for addressing bone defects and fostering bone regeneration.     

Self-Reliant Nanomedicine with Long-Lasting Glutathione Depletion Ability Disrupts Adaptive Redox Homeostasis and Suppresses Cancer Stem Cells

Bulk cancer cells and cancer stem cells (CSCs) harbor efficient and adaptive redox systems to help them resist oxidative insults arising from diverse therapeutic modalities. Herein, a tumor microenvironment (TME)-activatable nano-modulator capable of disrupting adaptive redox homeostasis, prepared by integrating FDA-approved xCT inhibitor sulfasalazine (SSZ) into pH-responsive hydroxyethyl starch-doxorubicin conjugate stabilized copper peroxide nanoparticles (HSCPs) is reported. Compared to poly(vinylpyrrolidone) (PVP)-stabilized copper peroxide nanoparticles, HSCPs exhibit superior physiological stability, longer circulation half-life, and higher tumor enrichment. Under an acidic TME, the active components inside HSCPs are productively released along with the disintegration of HSCPs. The specifically generated hydrogen peroxide (H₂O₂) from copper peroxide nanoparticles furnishes a constant power source for copper-mediated hydroxyl radical (•OH) production, serving as a wealthy supplier for oxidative stress. Meanwhile, the tumor-specific release of Cu²⁺ and SSZ can induce long-lasting glutathione (GSH) depletion via copper-mediated self-cycling valence transitions and SSZ-blocked GSH biosynthesis, thereby reducing the offsetting action of the antioxidant GSH against oxidative stress. As a result, this sustained oxidative stress potently restrains the growth of aggressive orthotopic breast tumors while suppressing pulmonary metastasis by eradicating CSC populations. The reported smart nanomedicine provides a new paradigm for redox imbalance-triggered cancer therapy.     

Design of Mitoxantrone-Loaded Biomimetic Nanocarrier with Sequential Photothermal/Photodynamic/Chemotherapy Effect for Synergized Immunotherapy

Metastatic triple-negative breast cancer (TNBC) has a poor prognosis and high mortality with no effective treatment options, and immunotherapy is highly anticipated as a potential treatment but is limited by the lack of tumor-infiltrating T lymphocytes in TNBC. Herein, red blood cell (RBC) membrane-camouflaged polyphosphoester (PPE) nanoparticles (RBC@PPE_MTO/PFA) are prepared as the nanocarriers of mitoxantrone (MTO) and perfluoroalkane (PFA) for synergized immunotherapy. The encapsulated MTO can generate heat and reactive oxygen species (ROS) to achieve photothermal and photodynamic therapy; moreover, ROS further triggers the self-accelerating release of MTO from the ROS-sensitive PPE core to enable chemotherapy. The RBC@PPE_MTO/PFA-mediated sequential photothermal/photodynamic/chemotherapy efficiently promotes the infiltration of CD8⁺ T cells into TNBC tumor tissue and synergizes the therapeutic activity of an immune checkpoint blockade antibody for metastatic TNBC treatment in distant and lung metastasis models. This biomimetic nanomedicine of MTO provides a convenient and available strategy to sensitize TNBC to immune checkpoint blockade antibody.     

Cuproptosis-Driven Enhancement of Thermotherapy by Sequentially Response Cu2-xSe via Copper Chemical Transition

Activation of cuproptosis pathway has been reported to hold great potential in the application of tumor treatment. But the efficacy of cuproptosis seriously limited by the insufficient accumulation in the tumor sites. Therefore, herein based on the strong stabilization effects of the metalloid element selenium (Se) on copper (Cu), a photothermic Cu_2-xSe nanoparticle encapsulated with bioresponsive dimethyl maleic anhydride (DMMA@Cu_2-xSe) as a copper-carrier to improve the copper accumulation in tumor is constructed, thus achieving cuproptosis-driven enhancement of thermotherapy. This nanosystem exhibits the enhancement of tumor cellular uptake by a weak acid-triggered charge-switching ability. Next step, the exposed Cu_2-xSe is oxidized and releases divalent copper by high-level oxide. Then, the abundant copper induces more dihydrolipoamide S-acetyltransferase oligomerization to down-regulate FDX1 and tricarboxylic acid cycle-related proteins, which leads to inhibiting aerobic respiration. Cuproptosis-induced mitochondrial damage further improves thermotherapy by up-regulating reactive oxygen species (ROS). In addition, the generated ROS also promotes copper release to strengthen cuproptosis, and eventually improves tumor thermotherapy in turn. In general, DMMA@Cu_2-xSe with sequentially triggered copper-release, efficient cuproptosis, and appropriate photothermal is a self-enhanced nanoplatform for cuproptosis-driven enhancement of thermotherapy.     

Injectable Self‐Healing Antibacterial Bioactive Polypeptide‐Based Hybrid Nanosystems for Efficiently Treating Multidrug Resistant Infection,Skin‐Tumor Therapy,and Enhancing Wound Healing

The surgical procedure in skin‐tumor therapy usually results in cutaneous defects, and multidrug‐resistant bacterial infection could cause chronic wounds. Here, for the first time, an injectable self‐healing antibacterial bioactive polypeptide‐based hybrid nanosystem is developed for treating multidrug resistant infection, skin‐tumor therapy, and wound healing. The multifunctional hydrogel is successfully prepared through incorporating monodispersed polydopamine functionalized bioactive glass nanoparticles (BGN@PDA) into an antibacterial F127‐ε‐Poly‐L‐lysine hydrogel. The nanocomposites hydrogel displays excellent self‐healing and injectable ability, as well as robust antibacterial activity, especially against multidrug‐resistant bacteria in vitro and in vivo. The nanocomposites hydrogel also demonstrates outstanding photothermal performance with (near‐infrared laser irradiation) NIR irradiation, which could effectively kill the tumor cell (>90%) and inhibit tumor growth (inhibition rate up to 94%) in a subcutaneous skin‐tumor model. In addition, the nanocomposites hydrogel effectively accelerates wound healing in vivo. These results suggest that the BGN‐based nanocomposite hydrogel is a promising candidate for skin‐tumor therapy, wound healing, and anti‐infection. This work may offer a facile strategy to prepare multifunctional bioactive hydrogels for simultaneous tumor therapy, tissue regeneration, and anti‐infection.     

Touchable Electrochemical Hydrogel Sensor for Detection of Reactive Oxygen Species-induced Cellular Senescence in Articular Chondrocytes

In this study, a reactive oxygen species (ROS)-responsive hydrogel sensor (PD/MnO₂ hydrogel) is developed that can efficiently detect senescent cells. Using immature murine articular chondrocytes with serial passages, the sensor can identify small interfering RNA (siRNA) knockdown of peroxisome proliferator-activated receptor-alpha (PPARα) based on the concentration of ROS in cells, simultaneously maintaining its balance via scavenging activity to prevent cartilage degradation in osteoarthritis (OA). The hydrogel sensor exhibits a change in electronic properties, with a distinct resistance from 201.9 kΩ for P0 to 362.9 kΩ for P3, and fluorescence off/on performance with an increase in passaging time. In vitro investigation using PPARα-specific siRNA reveals a correlation between pressure sensitivity and senescent activity, wherein an elevation in observed signal occurred (41.5%). In vivo analysis reveals significant decrease in degradation of the cartilage of both young, 3 months old aged, 18 months old, and PPARα^−/− mice compared to PPARα^+/+ mice based on safranin O stains. The expression level of interleukin-1β is reduced in the cartilage of aged PPARα^−/− mice after implantation with hydrogel, indicating the potential of PD/MnO₂ hydrogel as a therapeutic modality against OA.     

Silk-Inspired In Situ Hydrogel with Anti-Tumor Immunity Enhanced Photodynamic Therapy for Melanoma and Infected Wound Healing

Easy cancer recurrence and wound infections have been clinical challenges after surgical treatment of melanoma. Herein, a silk-inspired in situ gelation system containing methacrylated silk fibroin (SF) and chlorine e6 for improved cancer therapy with enhanced wound healing is developed. Favored by the macrophage recruitment capacity of the SF hydrogel, promising antitumor immune responses can be turned “on” via near infrared irradiation in a controllable manner to achieve combination therapy with photodynamic therapy to significantly suppress melanoma recurrence. Moreover, the effective photodynamic antibacterial activity of this bioactive system with the capacity of light-controllable modulating macrophage phenotype promotes remarkable tissue ingrowth with hair follicle regeneration for Staphylococcus aureus infected wound healing. Thus, this multifunctional silk-based hydrogel system, as a desirable wound dressing, provides a new platform for promising melanoma therapy and skin regeneration.     

Noncompressible Hemostasis and Bone Regeneration Induced by an Absorbable Bioadhesive Self-Healing Hydrogel

Bone bleeding and bone defects arising from trauma or bone tumor resection pose a great threat to patients and they are challenging problems to orthopedic surgeons. Traditional hemostatic materials are not suitable for bone fractures where compression cannot be applied, neither are they effective during surgeries where large amounts of body fluids prevent them from adhering to the large and irregular bone wound sites. This research introduces a catechol-conjugated chitosan (CHI-C) multi-functional hydrogel with adhesion, self-healing, cytocompatibility, hemocompatibility, and blood cell coagulation capacity. The hydrogel can be injected into internal and irregular bleeding sites and bone defective areas, and then rapidly self-heals (within 2 min) to an integrated hydrogel that fully fills the defective sites and strongly sticks to bleeding areas in the presence of body fluids during surgery. In vivo experiments using a rabbit ilium bone defect model demonstrate quick hemostasis after the hydrogel is applied and the blood loss is only ¼ compared to the untreated injuries. In addition, the bone regeneration is not interfered by the hydrogel and the bone defect is no longer visible with disappearance of the hydrogel after 4 weeks. This multi-functional hydrogel is potentially valuable for clinical applications towards tissue adhesion, hemostasis, and bone regeneration.     

Targeted Magnetic Resonance Imaging/Near-Infrared Dual-Modal Imaging and Ferroptosis/Starvation Therapy of Gastric Cancer with Peritoneal Metastasis

Accurate identification and visualization of peritoneal metastases (PM) are clinically essential to improving the prognosis for gastric cancer. However, owing to the multifocal spread of peritoneal metastasis nodules, small size, and close contact with adjacent organs, identifying and completely removing them during surgery is extremely challenging, resulting in cancer treatment failure and recurrence. This study develops a T₁-weighted magnetic resonance imaging (MRI) contrast agent (FeGdNP)-loaded indocyanine green/glucose oxidase (ICG/GOx) with conjugation of an RGD dimer (RGD2) and acid-labile polymer mPEG (FeGdNP-ICG/GOx-RGD2-mPEG). Compared with commercial Magnevist, the proposed FeGdNP-ICG/GOx-RGD2-mPEG shows a two to three-fold higher tumor ΔSNR in MRI of peritoneal metastasis and subcutaneous animal models. Compared with free ICG, the increased fluorescent signal of FeGdNP-ICG/GOx-RGD2-mPEG allows for the detection of tiny tumor metastatic nodules (<3 mm), and the removal of the peritoneum transplanted tumors. Abundant gluconic acid and H₂O₂ are generated during the GOx-mediated glucose depletion process in cancer cells, thereby enhancing Fenton reaction efficiency. Accumulated toxic ·OH can damage the mitochondrial function and induce the release of mitochondrial reactive oxygen species, which activates the ferroptosis pathway. The data indicate the potential of the nanoparticles for MRI preoperative diagnosis, intraoperative fluorescence-guided navigation, and ferroptosis tumor therapy.     

Injectable Adhesive Hydrogel as Photothermal-Derived Antigen Reservoir for Enhanced Anti-Tumor Immunity

Low vaccine immunogenicity and tumor heterogenicity greatly limit the therapeutic effect of tumor vaccine. In this study, a novel injectable adhesive hydrogel, based on thermosensitive nanogels containing catechol groups and loaded with in situ-forming MnO₂ nanoparticles, is constructed to overcome these issues. The concentrated nanogel dispersion transforms into an adhesive hydrogel in situ after intratumoral injection. The photothermal effect of the loaded MnO₂ nanoparticles induces immunogenic cell death to release mass autologous tumor-derived protein antigens under near-infrared irradiation, which act as ideal immune stimulating substances avoiding the problem of tumor heterogenicity and are captured by the in situ-forming adhesive hydrogel. The antigens-captured adhesive hydrogel acts as an “antigen reservoir” and releases these captured antigens to recruit more dendritic cells to stimulate an intensive and lasting anti-tumor immune response mediated by CD8⁺ T cells. The primary tumors can be almost completely disappeared within 4 days without relapse, and the growth of the distal tumors and rechallenged tumors are also effectively inhibited by the treatment with the injectable adhesive hydrogel-based photothermal therapy. Therefore, the proposed “antigen reservoir” strategy shows the great potential application as an in situ-forming personalized vaccine to enhancing the cancer immune therapy.     

Injectable,Micellar Chitosan Self-Healing Hydrogel for Asynchronous Dual-Drug Delivery to Treat Stroke Rats

Stroke is a common disease with high mortality worldwide. The endogenous neural regeneration during the intracerebral hemorrhage (ICH) stroke is restricted by the brain cavity, inflammation, cell apoptosis, and neural scar formation. Biomaterials serving as temporary supporting matrices are highly demanded as injectable implants for brain tissue regeneration. Herein, a chitosan micellar self-healing hydrogel (CM hydrogel) with comparable modulus (≈150 Pa) to brain, shape adaptability, and proper swelling (≈105%) is developed from phenolic chitosan (PC) and a micellar crosslinker (DPF). Two model drugs are individually packaged in the hydrophilic network and hydrophobic micelle cavities of CM hydrogel, and they feature asynchronous releasing kinetics, including a first-order rapid release for hydrophilic drug and a zero-order sustained release for hydrophobic drug. The dual-drug loaded CM (CMD) hydrogel delivers two clinical drugs corresponding to the anti-inflammatory and neurogenesis phases of the stroke to ICH rats through brain injection. The rats receiving CMD hydrogel show behavioral improvement (≈84% recovery) and balanced brain midline shift (≈0.98 left/right hemibrain ratio). Immunohistochemistry reveals neurogenesis (doublecortin- and nestin- positive cells) and evidence of angiogenesis (≈18 µm diameter vessels lined with CD31-positive cells). The injectable CMD hydrogel offers a novel asynchronous drug delivery platform for treating ICH stroke.     

Photothermo-Promoted Nanocatalysis Combined with H2S-Mediated Respiration Inhibition for Efficient Cancer Therapy

Nanocatalytic medicine has emerged as a promising method for the specific cancer therapy by mediating the interaction between tumor microenvironment biomarkers and nanoagents. However, the produced antitumor cell killing molecules, such as reactive oxygen species (ROS), by catalysis are insufficient to inhibit tumor growth. Herein, a novel kind of polyvinyl pyrrolidone modified multifunctional iron sulfide nanoparticles (Fe_1−xS-PVP NPs) is developed via a one-step hydrothermal method, which exhibits high photothermal (PT) conversion efficiency (η = 24%) under the irradiation of 808 nm near-infrared laser. The increased temperature further facilitates the Fenton reaction to generate abundant •OH radicals. More importantly, under an acidic (pH = 6.5) condition within tumor environment, the Fe_1−xS-PVP NPs can in situ produce H₂S gas, which is evidenced to suppress the activity of enzyme cytochrome c oxidase (COX IV) in cancer cells, contributing to inhibit the growth of tumor. Both in vitro and in vivo results demonstrate that the H₂S-mediated gas therapy in combination with PT enhanced ROS achieves excellent antitumor performance, which can open up a new approach for the design of gas-mediated cancer treatment.     

Fabrication of Thermoresponsive Hydrogel Scaffolds with Engineered Microscale Vasculatures

Precise fabrication of microscale vasculatures (MSVs) has long been an unresolved challenge in tissue engineering. Currently, light-assisted printing is the most common approach. However, this approach is often associated with an intricate fabrication process, high cost, and a requirement for specific photoresponsive materials. Here, thermoresponsive hydrogels are employed to induce volume shrinkage at 37 °C, which allows for MSV engineering without complex protocols. The thermoresponsive hydrogel consists of thermosensitive poly(N-isopropylacrylamide) and biocompatible gelatin methacrylate (GelMA). In cell culture, the thermoresponsive hydrogel exhibits an apparent volume shrinkage and effectively triggers the creation of MSVs with smaller size. The results show that a higher concentration of GelMA blocks the shrinkage, and the thermoresponsive hydrogel demonstrates different behaviors in water and air at 37 °C. The MSVs can be effectively fabricated using the sacrificial alginate fibers, and the minimum MSV diameter achieved is 50 µm. Human umbilical vein endothelial cells form endothelial monolayers in the MSVs. Osteosarcoma cells maintain high viability in the thermoresponsive hydrogel, and the in vivo experiment shows that the MSVs provide a site for the perfusion of host vessels. This technique may help in the development of a facile method for fabricating MSVs and demonstrates strong potential for clinical application in tissue regeneration.     

Bioresorbable Scaffolds with Biocatalytic Chemotherapy and In Situ Microenvironment Modulation for Postoperative Tissue Repair

New biomaterials with antitumor and tissue repair function have become increasingly important for the postoperative care of melanoma surgery, which could prolong the tumor-free survival of patients while simultaneously facilitating the reconstruction of the trauma tissue. For this purpose, a bioresorbable composite scaffold is designed which is fabricated by depositing therapeutic amorphous calcium carbonate (ACC)-based nanoformulations in gelatin/polycaprolactone (GP) nanofibers via electrospinning. The ACC nanoformulations are integrated with Fe²⁺-preactivated bleomycin to deliver biocatalytically enhanced therapeutic effect while the hydrolysable ACC contents can act as proton scavengers to ameliorate the tumor tissue acidity in situ, leading to sustained inhibition on tumor recurrence and metastasis. The acid-triggered ACC decomposition also releases Ca²⁺ to activate the downstream Wnt/β-catenin signaling pathways, which can cooperate with the healing effect of the GP substrate and accelerate wound regeneration. The nanoengineered scaffold can be useful as a supplementary treatment for the postoperative management of melanoma.     

A Cooperative Copper Metal–Organic Framework‐Hydrogel System Improves Wound Healing in Diabetes

Chronic nonhealing wounds remain a major clinical challenge that would benefit from the development of advanced, regenerative dressings that promote wound closure within a clinically relevant time frame. The use of copper ions has shown promise in wound healing applications, possibly by promoting angiogenesis. However, reported treatments that use copper ions require multiple applications of copper salts or oxides to the wound bed, exposing the patient to potentially toxic levels of copper ions and resulting in variable outcomes. Herein the authors set out to assess whether copper metal organic framework nanoparticles (HKUST‐1 NPs) embedded within an antioxidant thermoresponsive citrate‐based hydrogel would decrease copper ion toxicity and accelerate wound healing in diabetic mice. HKUST‐1 and poly‐(polyethyleneglycol citrate‐co‐N‐isopropylacrylamide) (PPCN) are synthesized and characterized. HKUST‐1 NP stability in a protein solution with and without embedding them in PPCN hydrogel is determined. Copper ion release, cytotoxicity, apoptosis, and in vitro migration processes are measured. Wound closure rates and wound blood perfusion are assessed in vivo using the splinted excisional dermal wound diabetic mouse model. HKUST‐1 NPs disintegrated in protein solution while HKUST‐1 NPs embedded in PPCN (H‐HKUST‐1) are protected from degradation and copper ions are slowly released. Cytotoxicity and apoptosis due to copper ion release are significantly reduced while dermal cell migration in vitro and wound closure rates in vivo are significantly enhanced. In vivo, H‐HKUST‐1 induced angiogenesis, collagen deposition, and re‐epithelialization during wound healing in diabetic mice. These results suggest that a cooperatively stabilized, copper ion‐releasing H‐HKUST‐1 hydrogel is a promising innovative dressing for the treatment of chronic wounds.     

Ultraeffective Cancer Therapy with an Antimonene‐Based X‐Ray Radiosensitizer

Nanoparticulate chemotherapeutics hold great potential for inducing reactive oxygen species (ROS) overproduction and exerting antihypoxic effects for efficient cancer radiotherapy. However, previous strategies for designing smart radiosensitizers necessitate the multistep incorporation of nanomaterials to achieve valuable radiosensitive outcomes, which causes unpredictable safety issues including poor decomposition and undefined biotransformations. Ultrathin antimonene nanoparticles (AMNPs) are demonstrated as new radiosensitizers that achieve an efficient radiochemotherapeutic effect through the induction of a strong oxidative stress response and their significantly high radiotoxicity in vivo. Analyzing the irradiation process of AMNPs indicates that irradiation accelerates photoelectron generation and the valence transition to toxic Sb₂O₃, leading to cancer cell apoptosis and S‐phase arrest. The tumor regression activity and concealed biotoxicity of the AMNPs in a melanoma mouse model enhance the applicability of antimonene to overcoming radioresistance by increasing ROS generation and normoxia. This new technology can extend the applications of antimonene as an effective radiosensitizer and can promote its clinical translation for tunable and effective radiosensitization in the future.     

PtCu Nanosonosensitizers with Inflammatory Microenvironment Regulation for Enhanced Sonodynamic Bacterial Elimination and Tissue Repair

Sonodynamic therapy (SDT) is considered a reliable replacement therapy to overcome the resistance to antibiotics and the limited tissue penetration of traditional photo-induced therapy. Herein, ultrasmall platinum-copper alloy nanoparticles (PtCu NPs) modified with poly (maleic anhydridealt-1-octadecene)-polyethylene glycol (C₁₈PMH-PEG) with high sonodynamic activity, strong catalytic ability, and good glutathione (GSH) depletion performance are synthesized for highly efficient bacterial elimination. PtCu NPs obtained through a thermal decomposition approach can generate high toxic singlet oxygen (¹O₂) under ultrasound (US) irradiation, showing good sonodynamic performance. Meanwhile, the partial oxygenation formed on the surface of PtCu NPs endows them with good Fenton-like catalytic performance and superior GSH-depleting ability, thus enhancing reactive oxygen species (ROS) generation. In vitro experiments confirm that the synthesized PtCu- NPs can not only efficiently kill both gram-positive and gram-negative bacteria but also eliminate staphylococcus aureus (S. aureus) infection through ROS generation and then accelerate wound healing in the S. aureus-infected wound model. Meanwhile, the copper ions released from PtCu NPs can promote cell migration and angiogenesis through the up-regulation of hypoxia inducible factor (HIF-1α) and platelet endothelial cell adhesion molecule (CD31). Finally, the S. aureus-induced deep-seated osteomyelitis infection and bone destruction were successfully inhibited by the PtCu-mediated combination therapy. Our work highlights a novel SDT strategy for enhanced sonodynamic bacteria elimination and tissue repair.     

Engineering of a Hollow-Structured Cu2−XS Nano-Homojunction Platform for Near Infrared-Triggered Infected Wound Healing and Cancer Therapy

Infection and malignant tumors are the most common diseases in people's daily life, which seriously threaten human health. Because of the frequent and extensive administration of antibiotics and chemodrugs, the prevalence of multidrug-resistant bacteria and tumor cells makes the conventional therapies less effective and even invalid. To overcome the repugnant dilemma, herein the authors devise and develop a hollow Cu_2−XS nano-homojunction (nano-HJ) platform for the effective eradication of both bacteria and tumors upon tissue-penetrable near-infrared (NIR) light irradiation. Hyaluronan (HA) is covalently decorated onto the nano-homojunctions (nano-HJs) surface to enhance their biocompatibility, tumor-targeting ability, and cutaneous wound healing capability. The decorated nano-HJs exert robust NIR-activatable bactericidal modality and accelerate the cutaneous regeneration of bacteria-invaded full-thickness wounds through the synergy of photothermal/photodynamic effects, glutathione depletion, and HA assistance. After loading anticancer drug doxorubicin in the cavity of nano-HJs, the antitumor therapy efficacy is greatly strengthened both in vitro and in vivo by the collaborative photo-chemotherapy. Accordingly, this work not only highlights the great promise of the Cu_2−XS nano-HJs in the treatment of bacteria-induced contagious diseases and malignant tumors but also opens up a new research direction for the biomedical application of homojunction nanoplatforms in the future.