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Intracellular Uptake and Morphological Changes of Thermoresponsive and Degradable Nanogels

Gauri P. Misra1, Mofya Diallo1, and Tao L. Lowe2. (1) Surgery, Penn State University College of Medicine, 500 University Drive, Hershey, PA 17033, (2) Departments of Surgery, Bioengineering, and Materials Science and Engineering, Pennsylvania State University, 500 University Drive, Hershey, PA 17033

There is a growing interest in polymeric nanogels for drug delivery and diagnostic applications because of unable chemical and physical properties [1]. Our group has been working on a novel polymeric nanogel system having both thermoresponsive and degradable properties [2]. The nanogels were synthesized by UV photopolymerization at 45 C using N-isopropyl acrylamide (NIPAAm) and a cross-linkable macromer, 2-hydroxyethylmethacrylate-lactate-dextran of varying mass ratios. The size and morphology, and hydrodynamic radii of the nanogels were studied by atomic force microscopy and dynamic light scattering, respectively. Time-dependent interaction of these nanogels with rat retinal precursor (R28) and human glioblastoma (U87) cells were investigated using atomic force microscopy, laser confocal microscopy, and flow cytometry techniques. The MTT cell viability data indicated non-toxic nature of the nanogels at 100 g/mL concentration. The nanogels with more hydrophilic macromer component showed higher cell viability compared with the nanogels with a high NIPAAm content. Both confocal microscopy and flow cytometry studies confirmed uptake of the nanogels by the R28 and U87 cells. The uptake of the one week degraded nanogels decreased in the case of R28 cells while the opposite occurred in the case of U87 cells. The AFM images revealed morphological changes in the nanogels in culture media after one week. The nanogels in R28 culture medium exhibited a strong association between the nanogels with time leading to an increase in size while the U87 medium did not show such behavior. These studies suggest that cell type and morphological changes of nanogels are important factors affecting cellular interaction of nanogels.

1. N.A. Peppas, Intelligent therapeutics: biomimetic systems and nanotechnology in drug delivery, Advanced Drug Delivery Reviews 56, 1529 (2004).

2. Xiao Huang, Gauri Misra, Amit Vaish, Bryan Sutermaster, and Tao Lu Lowe, Novel Nanogels with Both Thermoresponsive and Hydrolytically degradable Properties, Macromolecules, 2008 (in press).