Abstract
The major challenge in the therapeutic applicability of oligonucleotide-based drugs is the development of efficient and safe delivery systems. The carriers should be non-toxic and stable in vivo, but interact with the target cells and release the loaded oligonucleotides intracellularly. We approached this challenge by developing a light-triggered liposomal delivery system for oligonucleotides based on a non-cationic and thermosensitive liposome with indocyanine green (ICG) as photosensitizer. The liposomes had efficient release properties, as 90% of the encapsulated oligonucleotides were released after 1-minute light exposure. Cell studies using an enhanced green fluorescent protein (EGFP)-based splicing assay with HeLa cells showed light-activated transfection with up to 70%–80% efficacy. Moreover, free ICG and oligonucleotides in solution transfected cells upon light induction with similar efficacy as the liposomal system. The light-triggered delivery induced moderate cytotoxicity (25%–35% reduction in cell viability) 1–2 days after transfection, but the cell growth returned to control levels in 4 days. In conclusion, the ICG-based light-triggered delivery is a promising method for oligonucleotides, and it can be used as a platform for further optimization and development.
Highlights
Therapeutics based on oligonucleotides have significant potential for the treatment of a wide variety of diseases [1,2]
We have previously shown that the indocyanine green (ICG)-containing liposomes are functional in light-triggered release of small and large fluorescently labeled model compounds [16]
We suggest that the increased fluidity of cell membranes and consequent increase in cellular permeability by this delivery system is dependent on two factors: Firstly, the ability of ICG to diffuse into cellular membranes, and this way, to create leakiness
Summary
Therapeutics based on oligonucleotides have significant potential for the treatment of a wide variety of diseases [1,2]. The most investigated synthetic vectors for oligonucleotides are lipid-based nanoparticles [5,6,7] These carriers contain cationic lipids that enable high loading capacity by complexing with negatively charged oligonucleotides and efficient intracellular delivery by interacting with the negatively charged cell membranes. To improve the control and effectiveness of cytosolic delivery and drug release at the target site, systems that are activated by external or internal signals, such as temperature, pH, ultrasound, specific enzymes, magnetic field and light, have been developed [14,15]. We have previously shown that the ICG-containing liposomes are functional in light-triggered release of small and large fluorescently labeled model compounds [16]. Our aim was to investigate the effects of light induction and ICG on cellular delivery of oligonucleotides and liposomal oligonucleotides
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