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 [51922111, 51873208, 51503200]
- Science and Technology Development Fund, Macau SAR [0124/2019/A3]
This study designed and synthesized two water-soluble prodrugs, CPT-lysine and CPT-arginine, to improve the solubility and anti-tumor effect of CPT. The introduction of arginine into CPTR enabled mitochondria-specific delivery, enhancing cell apoptosis and anti-cancer effect.
Camptothecin (CPT) has attracted much attention due to its potent antitumor activities. However, the undesirable physicochemical properties, including poor water solubility, unstable lactone ring, and severe adverse effects, limit its further application. In this study, two water-soluble 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-specific delivery, which increased mitochondrial reactive oxygen species generation, induced mitochondria dysfunction, and enhanced cell apoptosis 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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