A Photothermal Polymeric\nPlatform for Efficient and\nSafe Gene Transfection: When Polyethylenimine Collaborates with Indocyanine\nGreen

Gene transfection, defined by the delivery of nucleic\nacids into\ncellular compartments, stands as a crucial procedure in gene therapy.\nWhile branched polyethylenimine (PEI) is widely regarded as the “gold\nstandard” for nonviral vectors, its cationic nature presents\nseveral issues, including nonspecific protein adsorption and notable\ncytotoxicity. Additionally, it often fails to achieve high transfection\nefficiency, particularly with hard-to-transfect cell types. To overcome\nthese challenges associated with PEI as a vector for plasmid DNA (pDNA),\nthe photothermal agent indocyanine green (ICG) is integrated with\nPEI and pDNA to form the PEI/ICG/pDNA (PI/pDNA) complex for more efficient\nand safer gene transfection. The negatively charged ICG serves a dual\npurpose: neutralizing PEI’s excessive positive charges to reduce\ncytotoxicity and, under near-infrared irradiation, inducing local\nheating that enhances cell membrane permeability, thus facilitating\nthe uptake of PI/pDNA complexes to boost transfection efficiency.\nUsing pDNA encoding vascular endothelial growth factor as a model,\nour system shows enhanced transfection efficiency in vitro for hard-to-transfect\nendothelial cells, leading to improved cell proliferation and migration.\nFurthermore, in vivo studies reveal the therapeutic potential of this\nsystem in accelerating the healing of infected wounds by promoting\nangiogenesis and reducing inflammation. This approach offers a straightforward\nand effective method for gene transfection, showing potentials for\ntissue engineering and cell-based therapies.