Abstract
Selective drug release at the tumor site contributes to the reduction of side effects caused by anticancer treatments. To achieve a selective drug release system in cancer cells, we designed a new prodrug in which the anticancer drug camptothecin (CPT) is linked to a trimethyl lock (TML) group by an ester bond. Evaluation of in vitro cytostatic activity and drug release kinetics of the CPT-TML nano-prodrugs revealed that the ester of CPT-TML was stable against hydrolysis due to the steric hindrance around the ester derived from the tertiary hydroxy group. In contrast, CPT was smoothly released via sterically hindered ester cleavage by lactonization of the activated TML group. This finding will help in the development of nano-prodrugs with high selectivity at tumor site.
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