Photoporation with Biodegradable Polydopamine Nanosensitizers Enables Safe and Efficient Delivery of mRNA in Human T Cells

Safe and efficient production of chimeric antigen receptor (CAR)-T cells is crucial importance for cell-based cancer immunotherapy. Physical transfection methods have quickly gained in the context transfecting T-cells, since they are readily compatible with different cell types a broad variety cargo molecules. In particular, nanoparticle-sensitized photoporation has been introduced recent years as gentle yet method to transiently permeabilize cells, allowing subsequent entry external molecules into cells. Gold nanoparticles (AuNPs) used most photothermal sensitizers because can easily form laser-induced vapor nanobubbles, phenomenon that shown be particularly permeabilizing However, AuNPs not biodegradable, clinical translation hampered. Here, first time, possibility nanobubbles from biocompatible polymeric reported. Compared electroporation, physical T 2.5 times more living mRNA transfected human obtained via sensitized by polydopamine nanoparticles. This shows viable approach efficiently producing therapeutic engineered T-cells at throughput exceeding 105 per second.