Enhanced Cellular Uptake through Nanotopography-Induced Macropinocytosis

Abstract

Efficient cellular uptake of biomolecules, including genetic material, mRNA, proteins, and nanoparticles, requires novel approaches to overcome inherent cellular barriers. Here, the study investigates how nanotopographical cues from nanoporous surfaces impact the uptake efficiency by cells. The results demonstrate notable enhancements in cellular uptake efficiency across a range of vectors when cells are exposed to nanoporous surfaces. The uptake process is found to be dependent on the size and morphology of the nanopores, reaching a peak efficacy with blind pores of 400 nm in size. Enhanced genetic transduction on nanoporous surfaces are observed for multiple vectors, including lentiviruses, baculoviruses, and mRNA molecules. The versatile nature of this approach allows co-transfection of cells with multiple mRNA vectors. Moreover, the nanoporous platform is used for efficient and fast manufacturing of Chimeric Antigen Receptor (CAR)-T cells through lentiviral transduction. Furthermore, the study pinpoints macropinocytosis as the predominant mechanism driving increased cellular uptake induced by the nanoporous surfaces. The introduced method for enhancing genetic transduction of cells has applications in immunotherapy research, drug delivery, and cell engineering.