MCM-41-like mesoporous silica nanoparticles (MSNs) grafted with a thermoresponsive copolymer of N-isopropylacrylamide were synthesized, fully characterized and tested to assess their efficiency as drug delivery systems. The hybrid nanoparticles were prepared by carrying out the optimized copolymer synthesis within the mesopores of MSNs after infiltration of monomers and initiator. Polymerization and grafting of the thermoresponsive copolymer occurred simultaneously by exploiting the reactive sites of the 3-methacryloxypropyltrimethoxysilane comonomer which carries a polymerizable group and alkoxysilane groups prone to condensation with surface silanols on silica. The grafted copolymer through its coil-to-globule transition acts as a gatekeeper for the temperature-controlled release of ibuprofen molecules loaded inside the pores. Significant difference in the quantitative release of ibuprofen was observed at 25 and 40 degrees C, which are below and above the lower critical solution temperature of the thermoresponsive copolymer. Importantly, the ordered mesoporous structure of the MSNs remained intact in all synthetic steps, loading of drug and during the in vitro release tests. (C) 2015 Elsevier B.V. All rights reserved.