Light-Triggered Cellular Delivery of Oligonucleotides

Pharmaceutics
Leena-Stiina KontturiEnrico Mastrobattista

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 pl...Continue Reading

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Citations

Feb 26, 2020·Pharmaceutics·Gaetano Lamberti, Anna Angela Barba
May 14, 2020·Polymers·Viktor Korzhikov-VlakhTatiana B Tennikova
Jul 3, 2021·Pharmaceutics·Christophe DeleheddeFederico Perche
Jun 27, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Enrico Mastrobattista
Jul 21, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Ahmed RefaatKarlheinz Peter

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Methods Mentioned

BETA
antisense oligonucleotide
dynamic light scattering
RNA Assay
transfection
transfect

Software Mentioned

Columbus

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