Glucose-modification of cisplatin to facilitate cellular uptake, mitigate toxicity to normal cells, and improve anti-cancer effect in cancer cells

• Published in: Journal of molecular structure Vol. 1203; p. 127361
• Main Authors: Quan, Li, Lin, Zuantao, Lin, Yuebin, Wei, Yanchun, Lei, Liu, Li, Yaxi, Tan, Gongjun, Xiao, Min, Wu, Tianfu
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 05.03.2020
• Subjects: Anti-cancer efficacy; Cisplatin; Glucose transport channel; Glucose-modification; Platinum(Ⅳ); Glucose-modification; Anti-cancer efficacy; Platinum(Ⅳ); Cisplatin; Glucose transport channel
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2019.127361

Cisplatin has been considered an effective anticancer drug clinically. However, drug resistance and side effects of toxicity on normal cells greatly diminish the anti-cancer outcome of cisplatin. In this study, glucose modification was conducted to improve cisplatin anti-cancer efficacy. Firstly, cisplatin was oxidized to c,c,t-[Pt(NH3)2Cl2(OH)2] and then a carboxyl group was introduced to obtain c,c,t-[Pt(NH3)2Cl2(OOCCH2CH2COOH)2] (Pt(IV)–COOH), and finally glucose was grafted onto Pt(IV)–COOH. The glucose modification of cisplatin opens the glucose transport channels (GTC) on the cell membrane for Pt drug. The opening of GTC increases the uptake of Pt drug for cells. This simple and effective modification strategy may not only mitigate toxicity to normal cells, but also increase the anti-cancer effect of Pt drugs. •Cisplatin modified by glucose improved anti-cancer efficacy of Pt drugs to cancer cells. To some extent, Pt(IV) prodrugs can reduce the side effects of Pt(Ⅱ) drugs.•As a Pt(IV) prodrug, Pt(IV)-glucose improved cell internalization by opening up and utilizing GTC and IC of cancer cells.•As a result, cellular uptake of Pt drug was increased, toxicity to normal cells was mitigated, and inhibition to cancer cells was improved.•Therefore, a synergistic enhancement of the anti-cancer efficacy has been achieved.