One step synthesis of monodisperse thiol-ene clickable polymer microspheres and application on biological functionalization

Abstract

Introducing clickable groups onto polymer microspheres allows the microspheres to be facilely functionalized via a click reaction. In this report, we have synthesized monodisperse PMMA microspheres with clickable double bonds on the surface by one-step RAFT-assisted dispersion photopolymerization using a cyclohexyl-containing macro-RAFT agent as a stabilizer. This macro-RAFT agent, named P(THPAA-b-AA)-TTC, was synthesized by RAFT-mediated block copolymerization of a cyclohexyl-containing monomer (THPAA, obtained by esterification of cis-1,2,3,6-tetrahydrophthalic with 2-hydroxyethyl acrylate) and acrylic acid. The obtained microspheres were analyzed by 1H NMR and Iodometric method, indicating that the content of carbon double bonds on the microspheres increased with increasing the amount of P(THPAA-b-AA)-TTC in the polymerization feed. We then used a thiolated biotin to perform the photo-click reaction with the cyclohexene double bond on the microspheres, thereby attaching the biotin unit onto the microspheres. The biotinylated PMMA microspheres were found to be able to effectively immobilize fluorescein isothiocyanate streptavidin (FITC-SAv) via the specific adsorption of biotin to streptavidin, and thus exhibited clear fluorescence under confocal microscope. This study provides a convenient and feasible way to prepare surface-functionalized microspheres, which has great potential in biological applications as well as other fields.