A camptothecin-based, albumin-binding prodrug enhances efficacy and safety in vivo

The albumin-based drug delivery system is an effective drug delivery strategy for traditional chemotherapeutic drugs that can improve their antitumour efficacies and reduce systemic toxicities. The camptothecin derivative CPTS0001 has excellent antitumour activity in vitro, but it shows toxicity and side effects in vivo. In this study, we report the synthesis and biological evaluation of the beta-glucuronidase-reactive albumin-binding prodrug Mal-glu-CPTS0001 based on quaternary ammonium. After intravenous administration, the compound covalently binds to plasma albumin through Michael addition, enabling it to accumulate in tumours, where tumour-associated beta-glucuronidase triggers the selective release of CPTS0001. This prodrug significantly reduced the toxicity of the parent drug, and the maximum tolerated dose was increased by 2.5 times. At the same time, this prodrug enhanced the selectivity in vivo and improved the preferential accumulation of prodrug in tumours. Notably, this prodrug exhibited excellent in vivo antitumour effects in a murine breast cancer xenograft model without visible pathological toxicity. (C) 2021 Elsevier Masson SAS. All rights reserved.

Automated summary

The study presented an albumin-based drug delivery system, synthesized an antitumor prodrug Mal-glu-CPTS0001, and demonstrated its in vivo antitumor effects. The prodrug covalently binds to plasma albumin, releases the drug in tumors, and achieves reduced toxicity and enhanced selectivity.