Thermo-sensitive microgel particles may exert a swelling force inside cells and influence on cell viability due to their volume transition in response to external temperature change. In this study, cross-linked poly(N-isopropylacrylamide) (PNIPAM) microgel particles with a thermo-responsive volume expansion ability were prepared by precipitation polymerization of NIPAM, poly(ethylene glycol) diacrylate and acrylic acid. To endow the microgel particles with enhanced cellular uptake and visualization, cell penetrating peptide TAT and fluorescent probe were further covalently immobilized. The cellular uptake, intracellular distribution and thermo-responsive cytotoxicity of the microgel particles were studied by co-culture with lung adenocarcinoma (A549) cells. The PNIAPM microgel particles were largely ingested by A549 cells and mainly located in lysosomes. TAT modification enhanced the cellular internalization of particles but did not alter their intracellular distribution. While the PNIPAM microgel particles did not show significant impact on cell viability at 37 degrees C, they caused cytotoxicity to some extent when being cultured at 25 degrees C for 4 h. Doxorubicin loaded PNIPAM microgel particles showed the strongest cytotoxicity when being cultured at 25 degrees C for 4 h, suggesting the combinational effect of intracellular volume expansion and drug release on cells. (C) 2014 Elsevier Inc. All rights reserved.