Free paclitaxel-loaded E-selectin binding peptide modified micelle self-assembled from hyaluronic acid-paclitaxel conjugate inhibit breast cancer metastasis in a murine model

Publication date: 7 August 2017 Source:International Journal of Pharmaceutics, Volume 528, Issues 1–2 Author(s): Xiaofeng Han, Xuerong Dong, Jing Li, Manyuan Wang, Lei Luo, Zhaoxia Li, Xuran Lu, Rui He, Rongsong Xu, Muxin Gong The present work seeks to construct a nanovehicle for the efficient suppression of breast cancer metastasis through targeting E-selectin on tumor vascular endothelial cells and hyaluronic acid-receptor on tumor cells. Herein, a new ligand-PEG-lipid conjugate, E-selectin binding peptide-polyethene glycol-1-octadecylamine (Esbp-PEG-OA), was used as the targeting molecule of micelle self-assembled form hyaluronic acid-paclitaxel (HA-PTX) conjugate. When loaded with free PTX, the micelles (Esbp-HA-PTX/PTX) exhibited nanoscale particle size with high drug-loading capacity (up to 31.5%). In vitro release study showed that the conjugated and entrapped PTX released simultaneously. Cellular uptake of micelles confirmed that Esbp-HA-PTX micelles could be specifically and efficiently internalized into E-selectin expressing human umbilical vein endothelial cells (HUVEC) and 4T1 breast cancer cells via receptor-meditated endocytosis. In vitro cytotoxicity assay further revealed that Esbp-HA-PTX/PTX micelles significantly improved the selectivity of PTX for killing the two cell types compared with PTX solution formulation. More importantly, Esbp-HA-PTX micelles raised the accumulation of payload in tumor through targeting two cell types in the tumor mic...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research