EGCG-enabled Deep Tumor Penetration of Phosphatase and Acidity Dual-responsive Nanotherapeutics for Combinatory Therapy of Breast Cancer

文献类型： 外文期刊

第一作者： Zhou, Mengxue

作者： Zhou, Mengxue;Zhou, Chuang;Lin, Zhiyuan;Wang, Ying;Zhu, Yin;Shi, Jiang;Tan, Junfeng;Guo, Li;Zhang, Yue;Peng, Qunhua;Dai, Weidong;Lv, Haipeng;Lin, Zhi;Zhou, Chuang;Zhao, Yanni;Geng, Huan;Huang, Zhiwei;Yu, Haijun

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关键词： chemo/chemodynamic therapy; EGCG; nanomedicine; TGF-beta signaling; triple-negative breast cancer

期刊名称：SMALL （ 影响因子：12.1； 五年影响因子：12.5 ）

ISSN： 1613-6810

年卷期： 2025 年 21 卷 14 期

页码：

收录情况： SCI

摘要： The presence of dense collagen fibers is a typical characteristic of triple-negative breast cancer (TNBC). Although these fibers hinder drug penetration and reduce treatment efficacy, the depletion of the collagen matrix is associated with tumor metastasis. To address this issue, epigallocatechin-3-gallate (EGCG) is first exploited for disrupting the dense collagenous stroma and alleviate fibrosis by specifically blocking the TGF-beta/Smad pathway in fibroblasts and tumor cells when intraperitoneally administrated in TNBC tumor-bearing mice. A methotrexate (MTX)-loaded dual phosphate- and pH-responsive nanodrug (pHA@MOF-Au/MTX) is next engineered by integrating Fe-based metal-organic frameworks and gold nanoparticles for improved chemo/chemodynamic therapy of TNBC. Surface modification with pH (low)-insertion peptide substantially enhanced the binding of the nanodrug to 4T1 cells owing to tumor stroma remodeling by EGCG. High-concentration EGCG inhibited glutathione peroxidase by regulating mitochondrial glutamine metabolism, thus facilitating tumor cell ferroptosis. Furthermore, sequential EGCG and pHA@MOF-Au/MTX treatment showed remarkable anti-tumor effects in a mouse model of TNBC, with a tumor growth inhibition rate of 79.9%, and a pulmonary metastasis rate of 96.8%. Altogether, the combination strategy developed in this study can improve the efficacy of chemo/chemodynamic therapy in TNBC and represents an innovative application of EGCG.

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