The major challenge in the therapeutic applicability of oligonucleotide-based drugs is the\ndevelopment of efficient and safe delivery systems. The carriers should be non-toxic and stable\nin vivo, but interact with the target cells and release the loaded oligonucleotides intracellularly.\nWe approached this challenge by developing a light-triggered liposomal delivery system for\noligonucleotides based on a non-cationic and thermosensitive liposome with indocyanine green\n(ICG) as photosensitizer. The liposomes had efficient release properties, as 90% of the encapsulated\noligonucleotides were released after 1-minute light exposure. Cell studies using an enhanced green\nfluorescent protein (EGFP)-based splicing assay with HeLa cells showed light-activated transfection\nwith up to 70%-80% efficacy. Moreover, free ICG and oligonucleotides in solution transfected cells\nupon light induction with similar efficacy as the liposomal system. The light-triggered delivery\ninduced moderate cytotoxicity (25%-35% reduction in cell viability) 1-2 days after transfection, but\nthe cell growth returned to control levels in 4 days. In conclusion, the ICG-based light-triggered\ndelivery is a promising method for oligonucleotides, and it can be used as a platform for further\noptimization and development.
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