Abstract
Affibody-conjugated RALA (affi-RA) are designed for delivering oligomeric 5-fluorodeoxyuridine (FUdR, metabolite of 5-FU) strand to raise the selectivity of 5-fluorouracil (5-FU), decrease its toxicity and improve its suboptimal therapeutic efficacy. The nanodrugs, FUdR@affi-RA, are spontaneously assembled by electrostatic interaction between positively charged affi-RA and negatively charged FUdR15 -strands (15 consecutive FUdR). FUdR@affi-RA exhibits excellent stability under simulated physiological conditions. Compared with free FUdR, FUdR@affi-RA shows excellent targeting and higher cytotoxicity in human epidermal growth factor receptor 2 (HER2) overexpressing gastric cancer N87 cells. Moreover, the anticancer mechanism studies reveal that FUdR@affi-RA enhances the expression and activity of apoptosis-associated proteins in the Bcl-2/Bax-caspase 8,9-caspase 3 apoptotic pathway induced by FUdR. This study indicates that the fusion vector, affi-RA, presents a promising delivery system platform for nucleoside analogue drugs and provides a new strategy for the development of therapeutics of cancer treatment.
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