Instant Intracellular Delivery of miRNA via Photothermal Effect Induced on Plasmonic Pyramid Arrays

Abstract MicroRNA (miRNA) therapeutics are a promising cancer treatment approach with high efficacy and low side effects. Although substantial progress regarding pharmacokinetics and pharmacodynamics of miRNAs is made, it remains challenging for effective and harmless intracellular delivery. In this study, instant and efficient intracellular delivery of miRNA against esophageal cancer via photothermal effects induced on plasmonic pyramid arrays is reported. An instantaneous high temperature can be generated (≈470 °C) on a plasmonic pyramid after laser stimulation (≈8 μs @640 nm), which is enough to disrupt the cell membranes to facilitate intracellular delivery of biocargos like miRNA. Within ≈150 μs after removal of laser stimulation, the pyramid temperature would decrease to ≈37 °C to avoid cell damage. By this approach, intracellularly delivery of miRNA‐185 to Taxol‐resistance esophageal cancer cells is successfully achieved within minutes with decent delivery efficiency (64%) and cell viability (>95%) are observed after optimization. Moreover, for combating drug resistance, 61.9% of KYSE30/Taxol cell is inhibited after laser‐stimulation via the combined effects of miR‐185 and Taxol with efficient intracellular delivery. This study provides a convenient intracellular delivery approach for large biocargos and a possible solution for overcoming cancer drug resistance.