Development of a folate receptor (FR)-targeted indenoisoquinoline using a pH-sensitive N-ethoxybenzylimidazole (NEBI) bifunctional cross-linker.

ABSTRACT: This Communication describes the synthesis and evaluation of a folate-conjugated drug delivery system (DDS) that incorporates an acid-sensitive N-ethoxybenzylimidazole (NEBI) bifunctional linker and a novel imidazole-containing indenoisoquinoline. Indenoisoquinolines are a class of TOP1 inhibitors that exhibit broad anticancer activity. Here, we examined whether a DDS that comprised an indenoisoquinoline attached to a folate moiety could help target activity to cancer cells that naturally overexpress the folate receptor (FR), thereby increasing the specificity of these compounds. Evaluation of the DDS revealed an 11-fold increased toxicity in folate receptor (FR)-overexpressing cells compared to in FR-knockdown cancer cells. Microscopy studies demonstrate enhanced internalization and local

SUBMITTER: Cao Y 

PROVIDER: S-EPMC4032194 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature