Abstract

An effective intracellular gene silencing strategy based on acoustically propelled nanowires modified with an interfering RNA's (siRNA) payload is described. The gold nanowires (AuNW) are wrapped with a Rolling Circle Amplification (RCA) DNA strand, which serves to anchor the siRNA therapy. The ultrasound (US)-powered propulsion of the AuNW leads to fast internalization and rapid intracellular movement and hence to an accelerated siRNA delivery and silencing response. To optimize the micromotor gene silencing procedure, the influence of motion, time, and siRNA dosage was investigated, leading up to a 94% silencing after few minutes treatment with US-propelled siRNA AuNWs, and to a dramatic (similar to 13-fold) improvement in the silencing response compared to the static modified nanowires. The ability of the nanomotor-based method for gene silencing has been demonstrated by measuring the GFP silencing response in two different cell lines (HEK-293 and MCF-7) and using detailed control experiments. The viability of the cells after the nanomotors treatment was examined using the MCF-7 cancer cell line. The use of DNA structures carried by the US propelled nanomotors for gene silencing represents an efficient tool that addresses the challenges associated with RNA transportation and intracellular delivery. Future implementation of nanomachines in gene therapy applications can be expanded into a co-delivery platform for therapeutics.