Influence of hydrolysis susceptibility and hydrophobicity of Sn-38 nano-prodrugs on their anticancer activity

Yoshitaka Koseki, Yoshikazu Ikuta, Liman Cong, Mayumi Takano, Hiroshi Tada, Mika Watanabe, Kohsuke Gonda, Takanori Ishida, Noriaki Ohuchi, Keita Tanita, Farsai Taemaitree, Anh Thi Ngoc Dao, Tsunenobu Onodera, Hidetoshi Oikawa, Hitoshi Kasai

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)


In the field of drug delivery, controllability of drug release site and duration are among the most important factors to manipulate the drug efficacy and side effects. In this paper, a series of nano-prodrugs (NPs) composed of anticancer agent SN-38 and various substituent groups were synthesized and fabricated. By increasing the hydrophobicity of the prodrug molecule (calculated logP values exceeded ca. 7) through changing the substituent group, the hydrolysis susceptibility of SN-38 NPs in mouse serum was drastically decreased, thus prolonged the blood retention time of the NPs. In light of this knowledge and the dispersion stability in aqueous media, SN-38 NP modified with cholesterol (SN-38-chol NPs) was selected to be the optimal candidate among the screened NPs. The in vivo pharmacological effect of SN-38-chol NP was about 10 times higher than irinotecan, the clinically used solubilized prodrug analog of SN-38. In addition, SN-38-chol NP has low side effects in evaluating intestinal damage. These NPs possess great potential for clinical application and promise to be a next-generation of drug for cancer treatment.

Original languageEnglish
Pages (from-to)1305-1313
Number of pages9
JournalBulletin of the Chemical Society of Japan
Issue number8
Publication statusPublished - 2019


  • Drug delivery
  • Hydrolysis susceptibility
  • Nano-prodrugs

ASJC Scopus subject areas

  • Chemistry(all)


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