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Influence of size and cross-linking density of microgels on cellular uptake and uptake kinetics.

The unique pH and temperature responsiveness of PNIPAM-based microgels make them a promising target for novel biomedical applications such as cellular drug delivery systems. However, we lack a comprehensive understanding of how the physico-chemical properties of microgels relate to their interaction with cells. Here, we show that HEK293T cells take up PNIPAM-based microgels on a second-to-minute time scale. Uptake rates are determined by microgel size and cross-linker content. Using fluorescence confocal live-cell microscopy, we observe microgel uptake in real-time and describe cellular uptake kinetics. Experiments reveal that small and less cross-linked microgels show faster uptake kinetics than microgels of larger size or higher cross-linker content. Only microgels that are larger than 800 nm in diameter and have cross-linking contents of 10 - 15 mol% do not show translocation into cells. Together, these results provide insight into microgel-cell interactions and generate quantitative information on the deterministic role of microgel architecture - i.e., size and rigidity - for uptake by a prototypical human cell line.