Influence of supramolecular encapsulation of camptothecin by cucurbit[7]uril: reduced toxicity and preserved anti-cancer activity

• Published in: MedChemComm 2016-01, Vol.7 (7), p.1392-1397
• Main Authors: Yang, Xue, Wang, Ziyi, Niu, Yanan, Chen, Xiuping, Lee, Simon M. Y, Wang, Ruibing
• Format: Article
• Language: English
• Subjects: Camptotheca; Danio rerio
• ISSN: 2040-2503; 2040-2511
• DOI: 10.1039/c6md00239k

Camptothecin (CPT), a natural antineoplastic agent that was originally isolated from the bark and stem of Camptotheca acuminata , targets a wide range of cancers by inhibition of topoisomerase I during DNA replication. In this study, we investigated the use of cucurbit[7]uril (CB[7]) for molecular encapsulation of CPT and the associated benefits of such encapsulation of CPT on its anti-cancer activity, and side effects have been systemically evaluated both in vitro and in vivo . The cytotoxicity of the free CPT and complexed CPT (CPT@CB[7]) was examined by MTT assay using both a healthy liver cell line (L02) and a liver cancer cell line (Bel-7402). Interestingly, both the free CPT and CPT@CB[7] demonstrated comparable anti-cancer efficacy in vitro on the cancer cell line Bel-7402, whereas CPT@CB[7] showed obviously lower toxicity on the healthy liver cell line L02, in comparison with the free CPT. The anti-cancer/anti-angiogenic activity and non-specific toxicity of both free CPT and CPT@CB[7] were further investigated in vivo with both transgenic and wild-type zebrafish models, showing again that CPT@CB[7] exhibited reduced non-specific toxicities with well-preserved anti-angiogenic activities, when compared with the free CPT. These results demonstrate that CB[7] may work as a functional excipient for alleviation of undesired side-effects of selected organic drugs. Encapsulation of camptothecin by cucurbit[7]uril significantly inhibited the systemic toxicities of the free drug, while maintaining its antitumor/anti-angiogenic activities.