High-throughput intracellular delivery is at the heart of numerous biomedical applications, including the delivery of membrane-impermeable drugs, gene editing, and regenerative medicine. Conventional viral-based strategies suffer from concerns over safety, cell viability, and high costs that have impeded their adoption. Non-viral strategies, such as cell membrane disruption-mediated approaches, have emerged as promising platforms. Direct, physical penetration of cell membranes using sharp nanostructures has been explored as a less destructive method. Here, we fabricate silicon nanovolcanos (SNVs) arrays for delivery of biomolecular cargos with high efficiency while maintaining high cell viability. Using multiple-patterning nanosphere lithography (MP-NSL), SNV structures were prepared with fully tunable geometric parameters (pitch, height, rim diameter, and hole depth), possessing hollow, syringe-like points at the apex, and less than 20 nm wall thickness. The sharp tips of SNVs enable penetration of cell membranes while minimizing disruption of cell functions. Biomolecular payloads loaded into the SNV cavities are delivered inside the cell upon penetration. We demonstrate successful delivery of membrane-impermeable enhanced green fluorescent protein plasmids with 80% transfection efficiency and near 90% cell viability after delivery of nucleic acids. With these advances in high transfection efficiency and viability, SNVs provide a versatile platform for a wide range of fundamental and clinical applications.

Silicon nanostructures for high-throughput intracellular gene delivery

256th National Meeting (2018)

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