In vitro biocompatibility of magnetic thermo-responsive nanohydrogel particles of poly(N-isopropylacrylamide-co-acrylic acid) with Fe3O4 cores: Effect of particle size and chemical composition

Biocompatibility is a critical factor in the design and development of candidate materials for biomedical use. This paper reports on the in vitro biocompatibility of magnetic stimuli-sensitive nanohydrogel particles composed of magnetite cores in poly(N-isopropylacrylamide-co-acrylic acid) shells referred to Fe3O4/P(NIPAAm-co-AAc). The AAc concentration and polymerization time were varied to fabricate magnetic nanoparticles with various AAc levels (1.80-2.37%) and particle sizes (74-213 nm). The P(NIPAAm-co-AAc) shell exhibited thermo-sensitive properties and the Fe3O4 core constituted 2.25-4.10% of the particles by weight. After a 2-day incubation of L929 cells with extract media that had been conditioned with various test samples, the cellular responses were monitored in terms of cell viability and growth. The Live/Dead assays showed that high levels of cellular viability (97.3-98.1%) were observed in all groups, indicating that none of the nanoparticles were cytotoxic. However, the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymetho-xyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assays demonstrated that the activity of mitochondrial dehydrogenase varied significantly in cultures exposed to different magnetic nanohydrogel particles. The murine fibroblasts exposed to the NIP-(AAc5.1-Fe)-2 sample, which contained the highest AAc content and largest particle sizes, were the least metabolically active. In contrast, the activity levels in the cultures treated with the low AAc content and small size particles (NIP-(AAc2.6-Fe)-1) were not significantly different from those in the control group. Our findings suggest that smaller magnetic stimuli-sensitive nanohydrogel particles with a lower AAc content may have little inhibitory impact on cell proliferation. Overall, the in vitro biocompatibilities of the nanoparticles depend on the chemical composition and size of the Fe3O4/P(NIPAAm-co-AAc) particles. (c) 2012 Elsevier B.V. All rights reserved.