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  • Title: The efficiency of tumor-specific pH-responsive peptide-modified polymeric micelles containing paclitaxel.
    Author: Zhao BX, Zhao Y, Huang Y, Luo LM, Song P, Wang X, Chen S, Yu KF, Zhang X, Zhang Q.
    Journal: Biomaterials; 2012 Mar; 33(8):2508-20. PubMed ID: 22197569.
    Abstract:
    The acidic pH in tumor tissues could be used for targeting solid tumors. In the present study, we designed a tumor-specific pH-responsive peptide H(7)K(R(2))(2), which could respond to the acidic pH in tumor tissues, and prepared H(7)K(R(2))(2)-modified polymeric micelles containing paclitaxel (PTX-PM-H(7)K(R(2))(2)) in order to evaluate their potential targeting of tumor cells and tumor endothelial cells and their anti-tumor activity in mice with tumor cells. PTX-PM-H(7)K(R(2))(2) was prepared by a thin-film hydration method. The in vitro release of PTX from PTX-PM-H(7)K(R(2))(2) was tested. The in vitro targeting characteristics of H(7)K(R(2))(2)-modified polymeric micelles on HUVEC (human umbilical vein endothelial cells) and MCF-7 (human breast adenocarcinoma cells) were evaluated. The in vivo targeting activity of H(7)K(R(2))(2)-modified polymeric micelles and the in vivo anti-tumor activity of PTX-PM-H(7)K(R(2))(2) were also investigated in MCF-7 tumor-bearing mice. The released PTX from the PTX-PM-H(7)K(R(2))(2) was not affected by the pH. The targeting activity of the H(7)K(R(2))(2)-modified polymeric micelles was demonstrated by in vitro flow cytometry and confocal microscopy as well as in vivo biodistribution. PTX-PM-H(7)K(R(2))(2) produced very marked anti-tumor and anti-angiogenic activity in MCF-7 tumor-bearing mice in vivo.
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