Lipoic acid-based nanoparticles improve mRNA delivery by helping cells take it in through sulfur-based uptake

In vivo experiments demonstrated high luciferase expression in the spleen and liver following intravenous injection of nanoparticle carriers.

• Conventional mRNA nanoparticle carriers face challenges in efficient release into the cytoplasm due to endosomal degradation.
• A novel class of lipoic acid derivative composite nanoparticles was designed to facilitate direct mRNA release into the cytoplasm.
• Surface disulfide bonds on the nanoparticles allow them to anchor to cell membranes, bypassing the endosomal pathway.
• In vitro optimization identified three formulations that were particularly effective for mRNA delivery.
• Thiol-mediated uptake was observed as the main pathway for internalization of the nanoparticles.

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