期刊
BOSNIAN JOURNAL OF BASIC MEDICAL SCIENCES
卷 22, 期 6, 页码 934-948出版社
ASSOC BASIC MEDICAL SCI FEDERATION BOSNIA & HERZEGOVINA SARAJEVO
DOI: 10.17305/bjbms.2022.7194
关键词
Camptothecin prodrug; reactive oxygen species; antitumor therapy
资金
- National Natural Science Foundation of China
- Science and Technology Development Fund, Macau SAR
- [51922111]
- [51873208]
- [51503200]
- [0124/2019/A3]
Designing and synthesizing water-soluble prodrugs improved the physicochemical properties of camptothecin, enhancing its anti-tumor effect, especially through mitochondria-specific delivery.
Camptothecin (CPT) has attracted much attention due to its potent antitumor activities. However, the undesirable physicochemical proper-ties, including poor water solubility, unstable lactone ring, and severe adverse effects, limit its further application. In this study, two water-solu-ble prodrugs, CPT-lysine and CPT-arginine, were designed and synthesized by conjugating lysine or arginine with CPT, improving its solubility, pharmacokinetic properties, and tumor penetration. Importantly, the introduction of arginine into CPTR contributed to the mitochondria -spe-cific delivery, which increased mitochondrial reactive oxygen species generation, induced mitochondria dysfunction, and enhanced cell apop-tosis and in vivo anti-cancer effect. This strategy is believed to hold great potential for organelle-specific synergistic anti-tumor therapy.
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