Dual-ferroptosis induction-based microneedle patches for enhanced chemodynamic/photothermal combination therapy against triple-negative breast cancer.
10.1016/j.apsb.2025.05.034
- Author:
Yujie WANG
1
;
Zhaoyou CHU
2
;
Peisan WANG
1
;
Tao LI
1
;
Yu JIN
1
;
Silong WU
1
;
Xiaowei SONG
3
;
Weinan ZHANG
1
;
Miaomiao YANG
4
;
Zhengbao ZHA
5
;
Haisheng QIAN
1
;
Yan MA
1
Author Information
1. School of Biomedical Engineering, Anhui Provincial Institute of Translational Medicine, Anhui Medical University, Hefei 230032, China.
2. Department of Critical Care Medicine, the First Affiliated Hospital of Anhui Medical University, Hefei 230032, China.
3. Department of Radiology, the First Affiliated Hospital of Anhui Medical University Research Center of Clinical Medical Imaging, Hefei 230032, China.
4. Department of Pathology, the First Affiliated Hospital of Anhui Medical University, Public Health Clinical Center, Hefei 230032, China.
5. School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, China.
- Publication Type:Journal Article
- Keywords:
Chemodynamic;
Ferroptosis;
Lipid peroxides;
Redox balance;
Triple-negative breast cancer
- From:
Acta Pharmaceutica Sinica B
2025;15(8):4210-4224
- CountryChina
- Language:English
-
Abstract:
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.
