A novel cyclodextrin-containing pH-responsive star polymer for nanostructure fabrication and drug delivery

A novel cyclodextrin-containing star polymer was synthesized by atom transfer radical polymerization using the arm-first approach. Copolymerization of a mixture of mono- and multi-methacrylate substituted cyclodextrin and 2-(dimethylamino) ethyl methacrylate initiated by poly(ethylene glycol) macroinitiator produced a core cross-linked star polymer. The star polymer could self-assemble into nanostructures via host guest interactions between the cyclodextrin polymer and hydrophobic guest molecules. The morphologies of these nanostructures showed regular transitions by altering the type of guest molecule, the ratio of star polymer to guest, and the pH of the solution. Furthermore, doxorubicin (DOX) was entrapped into the star polymer for the purpose of drug delivery. In vitro experiments demonstrated that the DOX-loaded nanoparticles could release their payload in response to the endosomal-pH after being internalized by HeLa cell via endocytosis. At high DOX concentration, DOX-loaded nanoparticles showed significantly higher cell cytotoxicity compared to the free drug. The results indicate that the star polymer has great promise for potential anticancer treatment.