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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. [ABSTRACT FROM AUTHOR]

Conventional bone scaffolds, which are mainly ascribed to highly active osteoclasts and an inflammatory microenvironment with high levels of reactive oxygen species and pro-inflammatory factors, barely satisfy osteoporotic defect repair. Herein, multifunctional self-assembled supramolecular fiber hydrogels (Ce–Aln gel) consisting of alendronate (Aln) and cerium (Ce) ions were constructed for osteoporotic bone defect repair. Based on the reversible interaction and polyvalent cerium ions, the Ce–Aln gel, which was mainly composed of ionic coordination and hydrogen bonds, displayed good injectability and autocatalytic amplification of the antioxidant effect. In vitro studies showed that the Ce–Aln gel effectively maintained the biological function of osteoblasts by regulating redox homeostasis and improved the inflammatory microenvironment to enhance the inhibitory effect on osteoclasts. Ribonucleic acid (RNA) sequencing further revealed significant downregulation of various metabolic pathways, including apoptosis signaling, hypoxia metabolism and tumor necrosis factor-alpha (TNF-α) signaling via the nuclear factor kappa-B pathway after treatment with the Ce–Aln gel. In vivo experiments showed that the clinical drug-based Ce–Aln gel effectively promoted the tissue repair of osteoporotic bone defects by improving inflammation and inhibiting osteoclast formation at the defect. Notably, in vivo systemic osteoporosis was significantly ameliorated, highlighting the strong potential of clinical translation for precise therapy of bone defects. [ABSTRACT FROM AUTHOR]

A multifunctional and potent sonosensitizer based on layered double hydroxides (LDHs) with a suitable bandgap and diverse immunological effects (activation of T cells and enhancement infiltration of T cells) was designed to facilitate high-performance SDT combined with immunotherapy. [Display omitted] Sonodynamic therapy (SDT) is a potential non-invasive therapeutic to overcome the limitation of depth and to enhance immunotherapy by converting "cold" to "hot" tumors. However, the intervention effect of SDT-induced hot tumors may not be sufficient to effectively enhance the effect of immunotherapy due to the intricate tumor microenvironment (TME). Herein, a multifunctional and potent sonosensitizer based on layered double hydroxides (LDHs) with a suitable bandgap and diverse immunological effects (activation of T cells and enhancement infiltration of T cells) was designed to facilitate high-performance SDT combined with immunotherapy. Briefly, Ca2+ was introduced into MgFe-LDH to construct MgCaFe-LDH to achieve excellent SDT performance, outstanding modulated TME ability, and a tremendous prognosis effect. The better SDT efficiency was attributed to the optimized electron structure and bandgap with increasing Ca2+ introduction. The regulation of the intricate TME by improving the hypoxic microenvironment and decreasing the concentration of glutathione (GSH) with reducibility to enhance oxidation stress further boosted the SDT effect. In addition, bioactive MgCaFe-LDH exhibited an excellent immunological function, resulting from Mg2+ and Ca2+ ions synergistically activating CD8+ and CD4+ T cells and enhancing the infiltration of T cells into tumor tissues. Moreover, the combined therapy with SDT and αCTLA-4 also displayed a suppressive effect on the bilateral tumor model. Our work highlights novel bioactive LDH sonosensitizers that integrate TME regulation, SDT, and immunological effects for efficient cancer therapy. [ABSTRACT FROM AUTHOR]

Oxygen‐deficient molybdenum oxide (MoOX) nanomaterials are prepared as novel nanosensitizers and TME‐stimulants for ultrasound (US)‐enhanced cancer metalloimmunotherapy. After PEGylation, MoOX‐PEG exhibits efficient capability for US‐triggered reactive oxygen species (ROS) generation and glutathione (GSH) depletion. Under US irradiation, MoOX‐PEG generates a massive amount of ROS to induce cancer cell damage and immunogenic cell death (ICD), which can effectively suppress tumor growth. More importantly, MoOX‐PEG itself further stimulates the maturation of dendritic cells (DCs) and triggeres the activation of the cGAS‐STING pathway to enhance the immunological effect. Due to the robust ICD induced by SDT and efficient DC maturation stimulated by MoOX‐PEG, the combination treatment of MoOX‐triggered SDT and aCTLA‐4 further amplifies antitumor therapy, inhibits cancer metastases, and elicits robust immune responses to effectively defeat abscopal tumors. [ABSTRACT FROM AUTHOR]

Oxygen‐deficient molybdenum oxide (MoOX) nanomaterials are prepared as novel nanosensitizers and TME‐stimulants for ultrasound (US)‐enhanced cancer metalloimmunotherapy. After PEGylation, MoOX‐PEG exhibits efficient capability for US‐triggered reactive oxygen species (ROS) generation and glutathione (GSH) depletion. Under US irradiation, MoOX‐PEG generates a massive amount of ROS to induce cancer cell damage and immunogenic cell death (ICD), which can effectively suppress tumor growth. More importantly, MoOX‐PEG itself further stimulates the maturation of dendritic cells (DCs) and triggeres the activation of the cGAS‐STING pathway to enhance the immunological effect. Due to the robust ICD induced by SDT and efficient DC maturation stimulated by MoOX‐PEG, the combination treatment of MoOX‐triggered SDT and aCTLA‐4 further amplifies antitumor therapy, inhibits cancer metastases, and elicits robust immune responses to effectively defeat abscopal tumors. [ABSTRACT FROM AUTHOR]

Multiple amplification of tumor oxidative stress has been demonstrated as efficient strategy to enhance the reactive oxygen species (ROS)‐mediated cancer therapy. Herein, vanadium‐based nanocatalysts, hydrogen vanadium bronzes (HXV2O5, for short HVO), were constructed and employed as novel biocatalysts for amplifying tumor oxidative stress and enhancing cancer catalytic therapy. Such HVO nanocatalysts harboring multivalent V element possessed multi‐functional catalytic activity in decomposing H2O2 into ⋅OH and depleting endogenous glutathione (GSH) to dually amplify tumor oxidative stress. Meanwhile, HVO nanocatalysts could also be activated by ultrasound to further triply amplify oxidative stress. The massive intracellular ROS caused mitochondrial dysfunction, DNA damage, cell cycle arrest, and cell proliferation inhibition, further realizing cancer cell death and tumor growth inhibition. Collectively, HVO nanocatalysts highlight the remarkable value of ROS‐mediated cancer therapies. [ABSTRACT FROM AUTHOR]

Multiple amplification of tumor oxidative stress has been demonstrated as efficient strategy to enhance the reactive oxygen species (ROS)‐mediated cancer therapy. Herein, vanadium‐based nanocatalysts, hydrogen vanadium bronzes (HXV2O5, for short HVO), were constructed and employed as novel biocatalysts for amplifying tumor oxidative stress and enhancing cancer catalytic therapy. Such HVO nanocatalysts harboring multivalent V element possessed multi‐functional catalytic activity in decomposing H2O2 into ⋅OH and depleting endogenous glutathione (GSH) to dually amplify tumor oxidative stress. Meanwhile, HVO nanocatalysts could also be activated by ultrasound to further triply amplify oxidative stress. The massive intracellular ROS caused mitochondrial dysfunction, DNA damage, cell cycle arrest, and cell proliferation inhibition, further realizing cancer cell death and tumor growth inhibition. Collectively, HVO nanocatalysts highlight the remarkable value of ROS‐mediated cancer therapies. [ABSTRACT FROM AUTHOR]

• (Mg@DOX) microrods were prepared by electrospinning technology for the combined MHT & chemotherapy under AMF. • Mg@DOX microrods exhibited good magnetothermal conversion efficiency and excellent penetration depth. • The controlled release of DOX could be realized under the eddy thermal effect. • Mg@DOX microrods with unique eddy thermal effects could achieve deep-seated tumor therapy through combined therapy. Magnetic hyperthermia therapy (MHT) is a minimally invasive cancer treatment to ablate tumors under an alternating magnetic field (AMF), possessing advantages including excellent tissue penetration, tumor-targeted selectivity, and negligible damage to the normal tissues. However, the low magnetothermal conversion efficiency (MTCE) of the magnetocaloric nanoagents limits its application. Herein, magnesium @ doxorubicin (Mg@DOX) microrods were prepared by electrospinning technology for the combined MHT and chemotherapy under AMF. The constructed Mg@DOX rods exhibited apparent magnetic field intensity-dependent temperature rise under AMF, stemming from the eddy thermal effect with good thermal stability, outstanding MTCE, and excellent penetration depth. Meanwhile, the DOX release increased with the prolonged magnetothermal time and the decreased pH value, thus realizing combined therapy. In vitro experiments showed that Mg@DOX microrods had an obviously cell-killing ability on account of the MHT and accelerated DOX release. In vivo experiments were further performed by implanting Mg@DOX microrods into 4T1 mouse breast tumors and the deep-seated rat liver tumors, showing excellent combined therapeutic effects. Moreover, Mg@DOX microrods showed excellent biocompatibility and displayed insignificant toxicity to the implanted animals. Our work highlighted the effective combined therapy of the unique eddy thermal effect of Mg@DOX microrods. [ABSTRACT FROM AUTHOR]