The effect of micro and nanotopography on endocytosis in drug and gene delivery systems.

Endocytosis is a fundamental biological process and is also the key mechanism for drug and non-viral gene delivery. The importance of topographical cues in modulating cell behaviors has become increasingly evident, but the influence of topography on endocytosis has however only been sparsely studied. We hypothesize that topography can enhance cellular endocytosis, and in turn the non-viral transfection efficiency. Nano- to microtopographical patterns were fabricated using nano-imprinting lithography (NIL). We first investigated if the substrate topographies could modulate endocytosis and in turn the cellular transfectability. Our results showed increased internalization of fluorescently labeled dextran by human mesenchymal stem cells (hMSCs) and monkey kidney fibroblasts (COS7) when they were cultured on micro- and nanopillars. When the hMSCs were introduced to green-fluorescent protein (GFP) encoding plasmid with Lipofectamine, highest transfection efficiency was observed in cells on nanopillars. Tunable detachable substrate topographies were also fabricated using NIL to promote endocytosis in different cell types, and our results show hMSCs phagocytosis of these polymeric structures. Besides being important in understanding the fundamental process of endocytosis, the current research results may also lead to applications utilizing nanotopography to enhance drug and gene delivery.