During the last years, the field of drug delivery has experienced a growing interest toward the so-called thermoresponsive polymers: synthetic materials that, due to the specific hydrophilic-lipophilic balance of their repeating units, exhibit a lower critical solution temperature (LCST) in water associated to a characteristic coil-globule transition. In this work, thermo-responsive amphiphilic block copolymers are synthesized via reversible addition-fragmentation transfer (RAFT) polymerization starting from thermo-responsive monomers and a hydrophobic biodegradable macromonomer, oligo(caprolactone) methacrylate (CL(3)MA), produced via ring opening polymerization (ROP). The obtained copolymers exhibit an interesting self-assembly behavior leading to nanoparticles (NPs) as long as temperature is kept below the LCST. Otherwise, once this value is overcome, the destabilization of the NPs causes the formation of hydrophobic superstructures that enhance the release of an entrapped lipophilic drug. This characteristic behavior has been systematically studied and related to the copolymer structure. In particular, the selfassembly behavior as well as temperature-triggered NP destabilization have been related to the relative length of the two blocks constituting the copolymers and to their hydrophilic-lipophilic balance (HLB). Finally, the efficacy of the thermoresponsive triggered drug release has been tested in the case of Paclitaxel (PTX). (C) 2016 Wiley Periodicals, Inc.