Surface-Mediated Intracellular Delivery by Physical Membrane Disruption

Effective and nondestructive intracellular delivery of exogenous molecules and other functional materials into living cells is of importance for diverse biological fundamental research and therapeutic applications, such as gene editing and cell-based therapies. However, for most exogenous molecules, the cell plasma membrane is effectively impermeable and thus remains the greatest barrier to intracellular delivery. In recent years, methods based on surface-mediated physical membrane disruption have attracted considerable attention. These methods exploit the physical properties of the surface to transiently increase the membrane permeability of cells come in contact thereto, thereby facilitating the efficient intracellular delivery of molecules regardless of molecule or target cell type. In this Review, we focus on recent progress, particularly over the past decade, on these surface-mediated membrane disruption-based delivery systems. According to the membrane disruption mechanism, three categories can be recognized: (i) mechanical penetration, (ii) electroporation, and (iii) photothermal poration. Each of these is discussed in turn and a brief perspective on future developments in this promising area is presented.