Abstract
Prostate tumor cell targeted peptide fragment conjugated to the nano drug delivery system is a promising strategy for prostate cancer therapy. In this work, an amphiphilic copolymer Chol-PEG-DUP1 (PEG-cholesterol conjugated with DUP1 peptide) has been synthesized and characterized by proton nuclear magnetic resonance spectrum ((1)H NMR). The paclitaxel (PTX) was encapsulated into the Chol-PEG-DUP1 micelles to obtain aqueous formulation with small particle size (within 200 nm) and high drug encapsulating efficiency. The DUP1 modified PTX micelle significantly enhanced the cytotoxicity of paclitaxel to PSMA negative prostate tumor cells (PC-3 cell) as demonstrated by MTT (IC50 = 15.8 μg/mL compared to 68.7 μg/mL of free PTX). Flow cytometry analysis and fluorescence images revealed the DUP1 peptide fragments on the surface of micelles increased drug uptake (2.08-fold) by PC-3 cells. Flow cytometry and immunoblotting analysis showed the DUP1 modified PTX micelle enhanced the mitochondrial apoptosis-inducing capacity of PTX to PC-3 cells. In conclusion, Chol-PEG-DUP1 modified micelle was a reasonable, facile, and economic drug delivery system to target the PSMA-negative prostate cancer.