As one of the most malignant tumors, metastatic melanoma essentially requires the regulation of the lysosomal cation channel, transient receptor potential mucolipin channel 1 (TRPML1), which is also involved in the participation of various ions, especially zinc ions. This perfectly aligns with the advanced therapeutic approach based on nanomaterials, because nanomaterials can easily integrate multiple metal elements to disrupt the internal homeostasis of various ions, eventually inhibiting the cell growth of metastatic melanoma. Hence, based on our previously proposed metalloptosis strategy, herein, zinc gallate-based nanoclusters (ZGOCs) containing both zinc and gallium were developed, capable of inducing metalloptosis. Responded to a weak-acid tumor microenvironment, ZGOCs could effectively release gallium ions that triggered ferroptosis through depleting glutathione and increasing lipid peroxidation levels. Moreover, the released zinc ions co-treated with ML-SA5, a TRPML-specific agonist, further promoted lysozincrosis. In addition, ZGOCs exhibited rechargeable afterglow luminescence, which facilitated in vivo clearer diagnostic images with high contrast for more accurate detection of tumor boundaries. Collectively, ZGOCs in combination with ML-SA5 significantly suppressed tumor growth with favorable biosafety, providing a promising metalloptosis-based strategy for the treatment of metastatic melanoma.

Microplastics can traverse human physiological barriers, infiltrate and accumulate in critical organs and tissues (e.g., brain, blood, and heart) over extended periods, posing significant threats to human health. While microplastic degradation in aquatic environments (e.g., contaminated water) has been extensively studied, research on bloodstream microplastic degradation remains largely unexplored, leaving a critical gap in remediation strategies. To fill this gap, we pioneered the fabrication of biocompatible magnetically driven Fe3O4@polydopamine (PDA)-lipase microrobots by functionalizing Fe3O4 nanoparticles with PDA and lipase for blood-borne microplastic degradation. In vitro blood experiments confirmed that this platform holds promise for future detoxification of circulating microplastics. The microrobots integrate synergistic functions: Fe3O4 enables magnetic responsiveness for precise movement control; PDA provides adhesive properties for robust microplastic binding; and lipase mediates enzymatic microplastic degradation. Guided by an external rotating magnetic field, the microrobots achieve targeted microplastic capture and in situ enzymatic degradation in blood without releasing harmful substances, addressing a pivotal safety concern for biomedical applications. Performance evaluations showed ~25% microplastic degradation efficiency in blood after 7 days of incubation. Additionally, the microrobots can be effectively recycled via magnetic separation postdegradation, reducing residuals and improving practicality. Hemolysis assays using rabbit blood and toxicity evaluations using human umbilical vein endothelial cells and immunofluorescence experiments confirmed their excellent biocompatibility and immunogenicity, an indispensable prerequisite for potential in vivo translation. As a proof-of-concept study, this work provides a promising biocompatible approach for blood microplastic degradation and clearance, simultaneously overcoming the technical challenge of blood-specific targeted degradation and meeting safety requirements, thus laying a foundation for microrobot-based mitigation of microplastic health hazards.

Wound infection remains a critical challenge in clinical practice, frequently leading to delayed healing and increased risks of complications. Herein, we first screened silver nanowires (Ag NWs) with excellent antibacterial, antioxidant, and cell migration-promoting properties from silver-based nanomaterials with distinct dimensional morphologies, including Ag nanowires (NWs), Ag nanoparticles (NPs), nitrogen-doped graphene (NGC) supported Ag nanoparticles (Ag NPs/NGC), and Ag single atoms (Ag1/NGC), as candidates for wound dressing applications. To further enhance therapeutic efficacy, we developed a composite film (Ag NWs@SF) by incorporating Ag NWs into silk fibroin (SF). Under near-infrared light, it generates localized heat to provide a synergistic antibacterial effect to accelerate wound healing. Interestingly, the robust electrical stimulation responsiveness of Ag NWs endows the film with the potential for real-time wound monitoring. This composite film demonstrates outstanding antibacterial activity against common wound pathogens, which maintains biocompatibility and fostering tissue regeneration. In vitro and in vivo studies reveal that the Ag NWs@SF membrane accelerates wound closure by stimulating cell migration, mitigating bacterial infection, and reducing inflammatory responses. These findings offer a novel approach for effective clinical wound management, potentially addressing the unmet clinical needs in infection combating and wound healing promoting.