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靶向上皮-间充质转化:用于预防肿瘤转移的金属有机网络纳米复合物。

Targeting epithelial-mesenchymal transition: Metal organic network nano-complexes for preventing tumor metastasis.

机构信息

Key Laboratory of Biomedical Polymers of Ministry of Education, Institute for Advanced Studies (IAS), Department of Chemistry, Wuhan University, Wuhan, 430072, PR China.

Key Laboratory of Biomedical Polymers of Ministry of Education, Institute for Advanced Studies (IAS), Department of Chemistry, Wuhan University, Wuhan, 430072, PR China; Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Key Laboratory for the Green Preparation and Application of Functional Materials of Ministry of Education, Hubei University, Wuhan, Hubei, 430062, PR China.

出版信息

Biomaterials. 2017 Sep;139:116-126. doi: 10.1016/j.biomaterials.2017.06.007. Epub 2017 Jun 6.

Abstract

Tumor metastasis is the leading cause of death in cancer patients, and epithelial-mesenchymal transition (EMT) is an essential step in tumor metastasis. Unfortunately, during the chemotherapy, EMT could be induced under the selective pressure of clinical cytotoxic drugs. Here, to solve this problem, we have synthesized multi-functional epigallocatechin gallate/iron nano-complexes (EIN) as a versatile coating material to improve conventional therapies. In vitro studies showed that this strategy could eliminate EMT-type cancer cells. Mechanism studies also revealed that EIN was able to down-regulate the downstream expression of metastasis-associated factors, decrease the migration ability of cancer cells and prevent cancer cells from gaining drug resistance. In vivo investigation revealed that EIN had superior ability to enhance the therapeutic effect of conventional nanomedicines and inhibit the EMT process. Our study indicates the promising use of EIN to make up for the deficiencies of chemotherapy may provide insights into systematic cancer therapy to overcome tumor metastasis and drug resistance.

摘要

肿瘤转移是癌症患者死亡的主要原因,上皮-间充质转化(EMT)是肿瘤转移的重要步骤。不幸的是,在化疗过程中,临床细胞毒性药物的选择压力会诱导 EMT 的发生。在这里,为了解决这个问题,我们合成了多功能表没食子儿茶素没食子酸酯/铁纳米复合物(EIN)作为一种通用的涂层材料来改善传统疗法。体外研究表明,该策略能够消除 EMT 型癌细胞。机制研究还表明,EIN 能够下调转移相关因子的下游表达,降低癌细胞的迁移能力,并防止癌细胞获得耐药性。体内研究表明,EIN 能够增强传统纳米药物的治疗效果,并抑制 EMT 过程。我们的研究表明,EIN 有望弥补化疗的不足,可能为系统癌症治疗提供新的思路,以克服肿瘤转移和耐药性。

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