Dual-ferroptosis induction-based microneedle patches for enhanced chemodynamic/photothermal combination therapy against triple-negative breast cancer

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 nanopar...

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Bibliographic Details
Main Authors: Yujie Wang, Zhaoyou Chu, Peisan Wang, Tao Li, Yu Jin, Silong Wu, Xiaowei Song, Weinan Zhang, Miaomiao Yang, Zhengbao Zha, Haisheng Qian, Yan Ma
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:Acta Pharmaceutica Sinica B
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Online Access:http://www.sciencedirect.com/science/article/pii/S2211383525003727
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Summary: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.
ISSN:2211-3835