GLUT1 targeting and hypoxia-activating polymer-drug conjugate-based micelle for tumor chemo-thermal therapy. (1st January 2021)

• Record Type: Journal Article
• Authors: Ma, Pengkai; Wei, Guijie; Chen, Jianhua; Jing, Ziqi; Wang, Xue; Wang, Zhijun
• Is Part Of: Drug delivery. Volume 28:Number 1(2021)
• Page Start: 2256
• Page End: 2267
• Publication Date: 2021-01-01
• Subjects: Polyprodrug -- micelle -- mitochondria targeting -- tumor microenvironment -- chemo-thermal therapy; Drug delivery systems -- Periodicals; Drug targeting -- Periodicals; 615.05
• DOI: 10.1080/10717544.2021.1992039
• Languages: English
• ISSNs: 1071-7544

Abstract

Abstract: 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.