GLUT1 targeting and hypoxia-activating polymer-drug conjugate-based micelle for tumor chemo-thermal therapy

Drug Delivery

Zhijun Wang¹  Guijie Wei²  Jianhua Chen²  Pengkai Ma²  Ziqi Jing²  Xue Wang² 

[1] Division of Interventional Radiology, Department of Geriatric Medicine & National Clinical Research Center of Geriatric Disease, the 2nd Medical Center of Chinese PLA General Hospital;School of Chinese Materia Medica, Beijing University of Chinese Medicine;

关键词: polyprodrug;    micelle;    mitochondria targeting;    tumor microenvironment;    chemo-thermal therapy;   

DOI  :  10.1080/10717544.2021.1992039

来源: DOAJ

【 摘 要 】

Purpose Mitochondria are closely correlated with the proliferation and metastasis of tumor for providing suitable micro-environment and energy supply. Herein, we construct a glucose transporter 1 (GLUT1) targeting and hypoxia activating polyprodrug-based micelle (Glu-PEG-Azo-IR808-S-S-PTX) for mitochondria-specific drug delivery and tumor chemo-thermal therapy. Results The micelle was characterized by hypoxia-sensitive PEG outer layer detachment, high photo-thermal conversion efficiency, and glutathione (GSH)-sensitive paclitaxel （PTX） release. It showed GLUT1 specifically cellular uptake and hypoxia-sensitive mitochondria targeting on A549 cell. In vivo fluorescence imaging confirmed the micelle also could selectively accumulate in tumor and its mitochondria on A549 tumor-bearing nude mice. Consequently, it not only exhibited higher cytotoxicity, apoptosis rate, and metastasis inhibition rate on A549 cells, but also better tumor growth and metastasis inhibition rate on tumor-bearing nude mice and lower whole-body toxicity. The mechanism might be caused by destroying mitochondria and down-regulating ATP production. Conclusion This study provided a GLUT1 targeting, hypoxia, and reductive responsive nanomedicine that hold the potential to be exploited for tumor therapy.

【 授权许可】

Unknown