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
作者： Zhou, Mengxue 1 ; Zhou, Chuang 1 ; Geng, Huan 3 ; Huang, Zhiwei 4 ; Lin, Zhiyuan 1 ; Wang, Ying 1 ; Zhu, Yin 1 ; Shi, Jiang 1 ; Tan, Junfeng 1 ; Guo, Li 1 ; Zhao, Yanni 2 ; Zhang, Yue 1 ; Peng, Qunhua 1 ; Yu, Haijun 5 ; Dai, Weidong 1 ; Lv, Haipeng 1 ; Lin, Zhi 1 ;
作者机构： 1.Chinese Acad Agr Sci, Tea Res Inst, Key Lab Tea Biol & Resource Utilizat, Minist Agr, Hangzhou 310008, Peoples R China
2.Shaanxi Univ Sci & Technol, Sch Food & Biol Engn, Xian 710021, Peoples R China
3.Zhejiang Univ, Affiliated Hosp 2, Dept Orthoped Surg, Sch Med, Hangzhou 310009, Zhejiang, Peoples R China
4.Lanzhou Univ, Frontiers Sci Ctr Rare Isotopes, MOE, Lanzhou 730000, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China
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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