4.8 Article

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

Journal

JOURNAL OF CONTROLLED RELEASE
Volume 339, Issue -, Pages 297-306

Publisher

ELSEVIER
DOI: 10.1016/j.jconrel.2021.09.040

Keywords

Antitumour; Chemotherapy; SN38; Drug delivery systems; Albumin

Funding

  1. Fundamental Research Funds for the Central Universities
  2. National Natural Science Foundation of China [22077034]

Ask authors/readers for more resources

The novel Mal-glu-SN38 prodrug showed selective delivery of SN38 to tumour sites and enhanced efficacy. With slower plasma clearance, increased drug exposure over time, and enhanced accumulation at the tumour site, Mal-glu-SN38 significantly delayed tumour growth after multiple doses, leading to an impressive reduction or even disappearance of tumours without observable side effects in 67% of mice.
Developing new therapeutic strategies that damage tumour cells without harming normal tissues is among the primary obstacles in chemotherapy. In this study, a novel 13-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 13-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

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.8
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available