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 t...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(Cu^(2+))and iron ions(Fe^(3+))were liberated from Cu-PB.The direct chelation of Cu^(2+)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 Cu^(2+)and Fe^(3+)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.展开更多
基金financially supported by the Research Fund of Anhui Institute of Translational Medicine(2022zhyx-B02,China)the Distinguished Youth of Natural Science Research Projects in Anhui Province Universities(2024AH020005,China)+1 种基金the Anhui Provincial Natural Science Foundation(2208085Y24,China)Open Project of Key Laboratory of Science and Engineering for the Multi-modal Prevention and Control of Major Chronic Diseases,Ministry of Industry and Information Technology(MCD-2023-1-14,China).
文摘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(Cu^(2+))and iron ions(Fe^(3+))were liberated from Cu-PB.The direct chelation of Cu^(2+)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 Cu^(2+)and Fe^(3+)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.
