High-efficiency intracellular delivery is at the heart of the future personalized medicine, with promising applications that include gene editing and modification, intracellular imaging, and drug delivery. Non-viral intracellular strategies have garnered significant attention to achieve high delivery efficiencies and increase cell viabilities, as well as to lower the costs compared with viral-based methods. Photothermal strategies, which use metal plasmonic structures and cavitation bubbles induced by nanosecond laser pulses, have made great strides towards achieving these goals. However, the fabrication process is complicated and hampered by low throughput. Here, we demonstrate the use of large-area arrays of plasmonic gold nanodisks for photothermal intracellular delivery. The Au nanostructures were fabricated using chemical lift-off lithography, which is a large-area, high-throughput, and low-cost patterning strategy developed recently in our group. In this way, nanostructures have been fabricated on a variety of substrates (<i>e.g.</i>, petri dishes) that facilitate <i>in situ</i> intracellular delivery in laboratory cell culture environments, demonstrating the ability to integrate this technique with existing medical devices. Nanosecond laser pulses were used to excite the plasmonic nanostructures and locally heat their surroundings, thereby creating transient pores in cell membranes that enable the delivery of biomolecular payloads. Devices were optimized by varying the size and spacing of the Au nanodisks as well as the incident pulse intensity. In doing so, we achieved delivery of 0.6 kDa Calcein into cells with efficiencies of up to 95% and cell viabilities up to 98%.

Photothermal intracellular delivery using large-area Au nanodisk arrays fabricated by chemical lift-off lithography

256th National Meeting (2018)

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