Nanoparticle-mediated photoporation - an emerging versatile physical drug delivery method

Facilitating the delivery of impermeable molecules into cells stands as a pivotal step for both basic research and therapeutic delivery. While current methods predominantly use nanoparticles or viral vectors, the exploration of physical phenomena, particularly light-based techniques, remains relatively under-explored. Photoporation, a physical method, employs either pulsed or continuous wave lasers to create transient pores in cell membranes. These openings enable the entry of exogenous, membrane-impermeable molecules into the cytosol while preserving cell viability. Poration can either be achieved directly through focusing a laser beam onto a cell membrane, or indirectly through the addition of sensitizing nanoparticles that interact with the laser pulses. Nanoparticle-mediated photoporation specifically has recently been receiving increasing attention for the high-throughput ability to transfect cells, which also has exciting potential for clinical translation. Here, we begin with a snapshot of the current state of direct and indirect photoporation and the mechanisms that contribute to cell pore formation and molecule delivery. Following this, we present an outline of the evolution of photoporation methodologies for mammalian and non-mammalian cells, accompanied by a description of variations in experimental setups among photoporation systems. Finally, we discuss the potential clinical translation of photoporation and offer our perspective on recent key findings in the field, addressing unmet needs, gaps, and inconsistencies.