Triple-negative breast cancer (TNBC) remains a refractory subtype of breast cancer due to its resistance to various therapeutic strategies. In this study, we introduce a "brake-release and accelerator-pressing" approach to engineer a microneedle patch embedded with copper-doped Prussian blue nanoparticles (Cu-PB) and the ferroptosis inducer sorafenib (SRF) for raised chemodynamic (CDT)/photothermal (PTT) combination therapy against TNBC. Upon transdermal insertion, the dissolving microneedles swiftly disintegrate and facilitate the release of SRF. Under gentle external light exposure, copper ions (Cu²⁺) and iron ions (Fe³⁺) were liberated from Cu-PB. The direct chelation of Cu²⁺ and the indirect suppression by SRF, collectively attenuate glutathione peroxidase 4 (GPX4) enzymatic function, destabilizing the cellular redox equilibrium (referred to as the "brake-release" strategy). The release of Cu²⁺ and Fe³⁺ ions instigates a Fenton/Fenton-like reaction within tumor cells, further yielding hydroxyl radicals and elevating reactive oxygen species (ROS) concentrations (referred to as the "accelerator-pressing" strategy). This overwhelming ROS accumulation, coupled with the impaired clearance of resultant lipid peroxides (LPO), ultimately triggers a robust ferroptosis cell death response. In summary, this study presents an innovative combinatorial therapeutic strategy based on dual-ferroptosis induction for TNBC, implying a promising therapeutic platform for developing ferroptosis-centered treatments for this aggressive breast cancer subtype.

Objective : To explore the application of ZnxNi1－xS@ DOX nanostructures in combined photothermal- chemotherapy treatment of tumors，and to provide new ideas for the study of tumor treatment methods． Methods: The morphology and elementary composition of ZnxNi1－xS nanostructures were characterized by scanning emission e- lectron microscopy and other methods．The photothermal properties of ZnxNi1－xS nanostructures were explored by infrared thermal camera．The release of DOX under different temperature and pH was investigated by fluorescence spectrophotometer．The biosafety of ZnxNi1－xS nanostructures and the in vitro antitumor properties of ZnxNi1－xS@ DOX nanostructures were investigated by MTT assay. Results : The as-prepared ZnxNi1－xS nanostructure had good dispersion and uniform size．The ZnxNi1－xS nanostructures had good photothermal effect．The drug release behavior showed temperature and pH responsiveness．The MTT assay showed that ZnxNi1－xS nanostructures were nontoxic to normal cells．ZnxNi1－xS@ DOX nanostructures could significantly inhibit the growth of tumor cells under near-infra- red illumination． Conclusion The as-prepared ZnxNi1－xS nanostructure has good biocompatibility，on the basis of which the ZnxNi1－xS@ DOX nanostructures achieve good antitumor performance，which can be used for combined photothermal-chemotherapy treatment of tumors.

Developing tumor-specific drug delivery systems with minimized off-target cargo leakage remains an enduring challenge. In this study, inspired from the natural cryptobiosis explored by certain organisms and stimuli-responsive polyphenol‒metal coordination chemistry, doxorubicin (DOX)-conjugated gelatin nanoparticles with protective shells formed by complex of tannic acid and Fe