Nanostructured Amphiphilic Star-Hyperbranched Block Copolymers for Drug Delivery

Abstract

A robust drug delivery system based on nanosized amphiphilic star-hyperbranched block copolymer, namely, poly­(methyl methacrylate-<i>block</i>-poly­(hydroxylethyl methacrylate) (PMMA-<i>b</i>-PHEMA) is described. PMMA-<i>b</i>-PHEMA was prepared by sequential visible light induced self-condensing vinyl polymerization (SCVP) and conventional vinyl polymerization. All of the synthesis and characterization details of the conjugates are reported. To accomplish tumor cell targeting property, initially cell-targeting (arginylglycylaspactic acid; RGD) and penetrating peptides (Cys-TAT) were binding to each other via the well-known EDC/NHS chemistry. Then, the resulting peptide was further incorporated to the surface of the amphiphilic hyperbranched copolymer via a coupling reaction between the thiol (−SH) group of the peptide and the hydroxyl group of copolymer by using <i>N</i>-(<i>p</i>-maleinimidophenyl) isocyanate as a heterolinker. The drug release property and targeting effect of the anticancer drug (doxorobucin; DOX) loaded nanostructures to two different cell lines were evaluated in vitro. U87 and MCF-7 were chosen as integrin α_vβ₃ receptor positive and negative cells for the comparison of the targeting efficiency, respectively. The data showed that drug-loaded copolymers exhibited enhanced cell inhibition toward U87 cells in compared to MCF-7 cells because targeting increased the cytotoxicity of drug-loaded copolymers against integrin α_vβ₃ receptor expressing tumor cells