Author:
Cao Zhiwen,Liu Rui,Li Yang,Luo Xinyi,Hua Zhenglai,Wang Xiangpeng,Xue Zeyu,Zhang Zhengjia,Lu Cheng,Lu Aiping,Liu Yuanyan
Abstract
AbstractThe chemotherapy of triple-negative breast cancer based on doxorubicin (DOX) regimens suffers from great challenges on toxicity and autophagy raised off-target. In this study, a conjugate methotrexate-polyethylene glycol (shorten as MTX-PEG)-modified CG/DMMA polymeric micelles were prepared to endue DOX tumor selectivity and synergistic autophagic flux interference to reduce systematic toxicity and to improve anti-tumor capacity. The micelles could effectively promote the accumulation of autophagosomes in tumor cells and interfere with the degradation process of autophagic flux, collectively inducing autophagic death of tumor cells. In vivo and in vitro experiments showed that the micelles could exert improved anti-tumor effect and specificity, as well as reduced accumulation and damage of chemotherapeutic drugs in normal organs. The potential mechanism of synergistic autophagic death exerted by the synthesized micelles in MDA-MB-231 cells has been performed by autophagic flux-related pathway.
Funder
Beijing Natural Science Foundation
Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine
Publisher
Springer Science and Business Media LLC
Cited by
3 articles.
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