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.

Postoperative metastatic recurrence and wound infection pose significant threats to survival after breast cancer (BC) surgery. To address these challenges, an ideal therapeutic strategy should incorporate minimally invasive multifunctional biomaterials capable of simultaneously preventing tumor recurrence and promoting wound healing. Herein, we report a novel 2-stage microneedle (MN) platform engineered via the integration of nanotechnology and tumor-microenvironment-responsive design. This system is fabricated using a stepwise casting strategy and features tip-to-base architecture equipped with on-demand smart nanocarriers for synergistic therapy against postoperative BC recurrence and wound complications. The MN consists of a photo-crosslinked hydrogel tip encapsulating chitosan-based self-assembled nanocarriers and a gelatin–polydopamine hydrogel backing layer. Owing to its hierarchical structural design, the MN exhibits excellent mechanical strength with a compression force of up to 4.48 N per needle, sufficient for efficient skin penetration. Moreover, the platform demonstrates sustained pH-responsive behavior and specific tumor microenvironment targeting, enabling controlled drug release. The MN also displays outstanding biocompatibility and multifunctional therapeutic properties, including antibacterial adhesion, self-healing capability, swelling performance, and biodegradability, greatly broadening its potential as a precision medicine tool. Both in vitro and in vivo studies validated the robust and integrated therapeutic efficacy of the MN system in suppressing metastatic BC recurrence and enhancing infected wound healing. This work provides a significant advance in the design of smart 2-stage MNs with comprehensive functionality for minimally invasive adjuvant therapy after BC surgery.

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.