DUP1 peptide modified micelle efficiently targeted delivery paclitaxel and enhance mitochondrial apoptosis on PSMA-negative prostate cancer cells.

Haining Chen,Jing Li,Xuehua Jiang,Lulu Cai,Xiang Li,Fengbo Wu

doi:10.1186/s40064-016-1992-0

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 (1H 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.

Highlights

Nowadays, prostate cancer is one of the main lethal cause from cancer patients worldwide, and more than one-third of newly diagnosed male cancer in Europe and USA was prostate cancer (Crawford 2003; Parkin et al 2001)
We have reported the fibroblast growth factor (FGF) fragment peptide modified micelles could significantly enhanced the cytotoxicity of paclitaxel for murine lewis lung cancer (LLC) cells, which were further confirmed by some subsequent experiments in vitro (Cai et al 2011)
All of the other multiple signals at 0.68–2.05 were the signals the protons in cholesterol. These results further showed that the conjugate had been successfully prepared

Summary

Introduction

Prostate cancer is one of the main lethal cause from cancer patients worldwide, and more than one-third of newly diagnosed male cancer in Europe and USA was prostate cancer (Crawford 2003; Parkin et al 2001). There were several treatment methods applied in the clinic, but none showed a survival benefit in hormone independent prostate cancer patients (Sternberg 2003). Prostate-specific membrane antigen (PSMA) as a member of trans-membrane folate hydrolase family, which could enhanced the expression level in prostate cancer tissue other than benign or neoplastic epithelial prostate cells (Bostwick et al 1998; Ross et al 2003). Chen et al SpringerPlus (2016) 5:362 other tissues (Renneberg et al 1999; Silver et al 1997) the Hu591 monoclonal antibody(mAb) targeting the PSMA extracellular domain, has been applied to the prostate cancer therapy (Liu et al 1997; Nanus et al 2003). Zitzmann et al, have reported a novel peptide DUP1 with specificity for PSMA-negative prostate tumor cell lines, such as DU-145 and PC-3, which was identified by phage display techniques

Methods

Results

Conclusion