1.Dual-ferroptosis induction-based microneedle patches for enhanced chemodynamic/photothermal combination therapy against triple-negative breast cancer.
Yujie WANG ; Zhaoyou CHU ; Peisan WANG ; Tao LI ; Yu JIN ; Silong WU ; Xiaowei SONG ; Weinan ZHANG ; Miaomiao YANG ; Zhengbao ZHA ; Haisheng QIAN ; Yan MA
Acta Pharmaceutica Sinica B 2025;15(8):4210-4224
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.
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