Light-responsive azobenzene-based glycopolymer micelles for targeted drug delivery to melanoma cells

Abstract

Light-responsive glycopolymer micelles were produced by the self-assembly of amphiphilic block copolymers containing azobenzene and beta-galactose units. These well-defined block copolymers were synthesised firstly by the RAFT polymerisation of an azobenzene methacrylate monomer (AzoMA) to produce two short azobenzene macroRAFT agents containing 7 and 15 monomer units. Chain extension with a second block of similar to 150 or similar to 250 sugar units comprising of a protected beta-galactose monomer (beta-AcGalEtMA) generated four block copolymers, which were converted to amphiphilic structures by deprotection of the acetyl groups on the sugar units. Micelles with well-defined sizes of 26-50 nm were produced by self-assembly in water. The azobenzene units isomerised very rapidly to their more polar cis isomers under UV irradiation, reaching the photostationary state within 2 min, with reversion to the trans state taking several hours in the dark. This transition to the more polar cis state is an important criteria for aiding expulsion of a hydrophobic payload. In cell studies, unloaded micelles showed low cytotoxicity, and micelles loaded with the model hydrophobic compound Nile red demonstrated high cellular uptake in human melanoma A375 cells, demonstrating their suitability as a potential drug delivery system for melanoma. (C) 2015 Elsevier Ltd. All rights reserved.