Hypothesis: How to encapsulate poly(N-isopropylacrylamide) (PNIPAM) mesoglobule cores by silica shells greatly affects the resultant nanoparticle structures. Incorporation of acrylamide (AM) unit into PNIPAM in combination with 3-glycidyloxypropyltrimethoxysilane (GLYMO, as a coupling agent) effectively induces nucleation and growth of silica on PNIPAM core surfaces, where the -NH2 of acrylamide reacts with the epoxide of GLYMO while GLYMO further participates in subsequent sol-gel reaction of tetraethyl orthosilicate (TEOS), thereby leading to desirable particle morphology. Experiments: PNIPAM-based core-silica shell nanoparticles were prepared by sol-gel reaction of TEOS and GLYMO in the presence of polymeric core particles. The major parameters investigated in a systematic fashion include acrylamide concentration and weight ratio of polymer:GLYMO:TEOS. GPC, DLS, DSC, FE-SEM, TEM, FTIR and TGA were then used to characterize polymeric cores and hybrid nanoparticles. Findings: The particle morphology was governed primarily by the acrylamide content and the weight ratio of PNIPAM/AM:GLYMO:TEOS, and desirable hybrid nanoparticles with narrow particle size distribution were achieved. The LCST of PNIPAM-based mesoglobules increases with increasing acrylamide content. Encapsulation of PNIPAM-based mesoglobules with silica also reduces their thermosensitivity. This is the first report of developing a novel approach to prepare PNIPAM-based mesoglobule core-silica shell nanoparticles with controllable particle morphologies. (C) 2018 Elsevier Inc. All rights reserved.