A reversible addition-fragmentation chain transfer (RAFT) agent was directly anchored onto Fe3O4 nanoparticles in a simple procedure using a ligand exchange reaction of S-1-dodecyl-S'-(alpha,-alpha'-dimethyl-alpha"-acetic acid)trithiocarbonate with oleic acid initially present on the surface of pristine Fe3O4 nanoparticles. The RAFT agent-functionalized Fe3O4 nanoparticles were then used for the surface-initiated RAFT copolymerization of N-isopropylacrylamide and acrolein to fabricate structurally well-defined hybrid nanoparticles with reactive and thermoresponsive poly(N-isopropylacrylamide-co-acrolein) shell and magnetic Fe3O4 core. Evidence of a well-controlled surface-initiated RAFT copolymerization was gained from a linear increase of number-average molecular weight with overall monomer conversions and relatively narrow molecular weight distributions of the copolymers grown from the nanoparticles. The resulting novel magnetic, reactive, and thermoresponsive core-shell nanoparticles exhibited temperature-trigged magnetic separation behavior and high ability to immobilize model protein BSA. (C) 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 542-550, 2010