Oxygen vacancy-rich CoSn(OH)6/FeS2 heterostructure-based microneedles for combinatorial cancer therapy via activation of ferroptosis and apoptosis.

Resistance to apoptosis-based cancer therapies severely limits treatment efficacy. Ferroptosis, a distinct form of regulated cell death driven by lipid peroxidation, offers a promising alternative to overcome such resistance. Herein, we developed an innovative microneedle patch system (CFA-MN) incorporating an oxygen vacancy-rich hollow CoSn(OH)₆/FeS₂ (CF) heterostructure, combined with the alkyl radical initiator 1,2-bis(2-(4,5-dihydro-1Himidazol-2-yl)propan-2-yl) diazene dihydrochloride, to achieve cooperative apoptosis-ferroptosis cancer therapy. The CF heterostructure, synthesized via alkaline etching and solvothermal methods, exhibited abundant oxygen vacancy, enhancing reactive oxygen species generation under 808 nm laser irradiation. In the tumor microenvironment, FeS₂ facilitated controlled H₂S release, inhibiting epithelial-mesenchymal transition and promoting apoptosis. Concurrently, Fe²⁺-mediated Fenton reactions led to lipid peroxide accumulation, triggering ferroptosis. The CFA-MN patch exhibited robust mechanical strength and rapid dissolution for precise delivery and controlled release. In vitro and in vivo results demonstrated significant tumor inhibition through combined apoptosis and ferroptosis pathways. This work highlights the potential of CFA-MN as a multifunctional platform to overcome chemoresistance and improve breast cancer treatment outcomes.