MTX-PEG-modified CG/DMMA polymeric micelles for targeted delivery of doxorubicin to induce synergistic autophagic death against triple-negative breast cancer

Breast Cancer Research

Research

Cheng Lu¹  Zhengjia Zhang²  Xinyi Luo²  Zhenglai Hua²  Yuanyan Liu²  Zeyu Xue²  Rui Liu²  Xiangpeng Wang²  Yang Li²  Zhiwen Cao³  Aiping Lu⁴ 

[1] Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, 100700, Beijing, China;School of Chinese Materia Medica, Beijing University of Chinese Medicine, 100029, Beijing, China;School of Chinese Materia Medica, Beijing University of Chinese Medicine, 100029, Beijing, China;Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, 100700, Beijing, China;School of Chinese Medicine, Hong Kong Baptist University, Kowloon,, Hongkong, China;

关键词: Triple-negative breast cancer;    Autophagy;    Doxorubicin;    Chitosan;    Micelles;   

DOI  :  10.1186/s13058-022-01599-9

 received in 2022-07-26, accepted in 2022-12-19,  发布年份 2022

来源: Springer

【 摘 要 】

The 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.

【 授权许可】

CC BY   
© The Author(s) 2023

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