title: Galactose-decorated cross-linked biodegradable poly(ethylene glycol)-b-poly(ε-caprolactone) block copolymer micelles for enhanced hepatoma-targeting delivery of paclitaxel.
abstract: The inferior in vivo stability of micellar drugs has been a prime challenge for their application in targeted drug delivery. Here we report on novel galactose-decorated covalently cross-linked biodegradable micelles based on photo-cross-linkable poly(ethylene glycol)-b-poly(acryloyl carbonate)-b-poly(ε-caprolactone) (PEG-PAC-PCL) and galactose-conjugated PEG-PCL (Gal-PEG-PCL) copolymers for enhanced hepatoma-targeting delivery of paclitaxel (PTX). The molecular weight of PEG in Gal-PEG-PCL was higher than that in PEG-PAC-PCL, thereby fully exposing Gal ligands at the micellar surface. These micelles, either with or without loading of PTX, were readily cross-linked by UV irradiation to afford micelles with small sizes (ca. 79-94 nm) and enhanced stability. The in vitro release studies confirmed that drug release from cross-linked micelles was significantly inhibited. Interestingly, MTT assays showed that Gal-decorated PTX-loaded cross-linked micelles retained a high antitumor activity in HepG2 cells, which was much more effective than PTX-loaded cross-linked micelles without Gal ligands and comparable to Gal-decorated PTX-loaded non-cross-linked micelles. Remarkably, the preliminary in vivo antitumor efficacy studies in SMMC-7721 tumor (human hepatoma)-bearing nude mice revealed that Gal-decorated PTX-loaded cross-linked micelles inhibited the growth of the human hepatoma more effectively than PTX-loaded cross-linked micelles as well as Gal-decorated PTX-loaded non-cross-linked micelles. These results indicate that Gal-decorated cross-linked PEG-PCL micelles have great potential in liver tumor-targeted chemotherapy.
authors: Biomedical Polymers Laboratory, Department of Polymer Science and Engineering, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, 215123, PR China.
authors: Rui
authors: R
authors: Yang
authors: Fenghua
authors: F
authors: Meng
authors: Shoubao
authors: S
authors: Ma
authors: Fushi
authors: F
authors: Huang
authors: Haiyan
authors: H
authors: Liu
authors: Zhiyuan
authors: Z
authors: Zhong
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000627:therapeutic use; D001672:Biocompatible Materials; D004337:Drug Carriers; D005026:Ethylene Glycols / Q000737:chemistry*; D005690:Galactose / Q000737:chemistry*; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008823:Micelles; D017239:Paclitaxel / Q000008:administration & dosage* / Q000627:therapeutic use; D011091:Polyesters / Q000737:chemistry*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001672:Biocompatible Materials; D004337:Drug Carriers; D005026:Ethylene Glycols; D008823:Micelles; D011091:Polyesters; C476300:poly(epsilon-caprolactone)-b-poly(ethylene glycol); D017239:Paclitaxel; D005690:Galactose