Ultrasound-aided Cellular Uptake and Endosomal Escape of Nanoparticles via the Membrane Surface Redox Reaction

Cellular uptake and endosomal escape are two critical biological barriers to nanoscale drug delivery. The exofacial thiols at cell surface have been previously reported to simultaneously overcome these two barriers via the thiol-disulfide/diselenide exchange reaction. However, the power of such approach for nanomedicine delivery enhancement was limited. To address the above issue, we employed the mechanical force(ultrasound) that could significantly enhance the kinetics of thiol-disulfide/diselenide exchange reactions, and then the delivery efficiency. The discovery in the current work opens new avenues of tailored nanomedicine design to circumvent the delivery hurdles.