Dual-functionalizable thiolactone-containing polymer brush-coated magnetic nanoparticles: 'Clickable' and redox-responsive platforms

Polymer brush-coated magnetic nanoparticles have been used in many applications, from localized drug delivery to imaging. In this study, polymer brush-coated iron oxide magnetic nanoparticles were synthesized using reversible addition-fragmentation chain transfer polymerization, and the dual-reactive feature was added to the polymeric coating by employing thiolactone units as side chains. In particular, first, thiolactone-containing N,Ndimethylacrylamide-based copolymers bearing a catechol end group were synthesized. A 'graft-to' approach was investigated to anchor these polymers onto the surface of magnetic iron oxide nanoparticles. Alternatively, to increase the amount of polymer coating, a 'graft-from' approach was followed, where a trithiocarbonate-based chain transfer agent group anchored to the nanoparticle using a catechol group was employed to grow polymer brushes. After obtaining the dual-functionalizable polymer brush-coated nanoparticles, the thiolactone group was reacted with an azide group containing amine to obtain a clickable group, and the newly formed thiol group was capped with pyridyl disulfide to obtain a thiol-exchangeable unit. A fluorescent thiol-bearing hydrophobic dye was conjugated onto the polymer-coated nanoparticles using a thiol-disulfide exchange reaction. The clickable azide groups were reacted with a cell adhesive cyclic peptide using the metal-free strain-promoted azide-alkyne cycloaddition (SPAAC) reaction. It was demonstrated that the fluorescent nanoparticles with the targeting group were internalized preferentially by breast cancer cells. One can envision that such dualfunctionalizable polymer brush-coated magnetic nanoparticles would be attractive nanomaterials for a variety of biomedical applications.