Universal Strategy of Efficient Intracellular Macromolecule Directional Delivery Using Photothermal Pump Patch

The development of a highly efficient, nondestructive, and in vitro/vivo-applicable universal delivery strategy of therapeutic macromolecules into desired cells and tissues is very challenging. Photothermal methods have advantages in intracellular delivery, particularly in in vivo manipulation. However, the inability of directional transmission of exogenous molecules limits their delivery efficiency. Here, a photothermal pump (PTP) patch with numerous "exogenous molecular reservoirs" is reported. Under a laser, the cell membrane ruptures, while "exogenous molecular reservoirs" shrink, resulting in a directional exogenous molecule delivery into cells for a high-efficient intracellular delivery. The PTP patches are considered a universal structure for a highly efficient, nondestructive, and in-vitro/vivo-applicable intracellular macromolecule delivery. Under in vivo transdermal intracellular delivery conditions, the target genes are efficiently and noninvasively delivered into epidermal and dermal cells through the PTP patch and exosomes produced by the epidermal cells, respectively. The PTP patch provides a new strategy for a high-efficiency, nondestructive, and in-vitro/vivo-applicable macromolecule delivery.