SN38-based albumin-binding prodrug for efficient targeted cancer chemotherapy.

Abstract

Developing new therapeutic strategies that damage tumour cells without harming normal tissues is among the primary obstacles in chemotherapy. In this study, a novel β-glucuronidase-sensitive albumin-binding prodrug was designed and synthesized to selectively deliver the drug SN38 to tumour sites and maximize its efficacy. After intravenous administration, the prodrug Mal-glu-SN38 covalently bound to plasma albumin through the Michael addition, enabling it to accumulate in the tumour and release SN38 when triggered by extracellular β-glucuronidase. Compared to irinotecan, Mal-glu-SN38 displayed a slower plasma clearance and increased drug exposure over time. Moreover, Mal-glu-SN38 caused an increase in tumour-site accumulation of both the albumin-prodrug conjugate and free SN38 released from albumin conjugate when compared with irinotecan. After administration of multiple doses, Mal-glu-SN38 also significantly delayed the tumour growth, resulting in an impressive reduction or even disappearance of tumours (67% of mice cured) without causing any observable side effects.

• Authors: Ying Huang, Lei Wang, Zhiyang Cheng, Biyu Yang, Jiahui Yu, Yi Chen, Wei Lu
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 339 Pg. 297-306 (11 10 2021) ISSN: 1873-4995 [Electronic] Netherlands
• PMID: 34619226 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• Albumins
• Prodrugs
• Irinotecan
• Camptothecin

Topics

• Albumins
• Animals
• Camptothecin
• Cell Line, Tumor
• Drug Delivery Systems
• Irinotecan
• Mice
• Neoplasms (drug therapy)
• Prodrugs