Lipidoid iron oxide nanoparticles are a platform for nucleic acid delivery to the liver
BULLETIN OF RUSSIAN STATE MEDICAL UNIVERSITY(2019)
Abstract
Targeted delivery of antisense drugs is a promising technology which can provide a platform for the development of highly effective therapeuticals against a broad range of diseases. Insufficient stability of RNA in biological media coupled with hydrophilicity that prevents the molecule from penetrating cell membranes considerably limit RNA application in clinical practice. The aim of this work was to design a system for antisense drug delivery to liver hepatocytes using lipidoid magnetic nanoparticles (LNP). Nanocubes (NC) with average sizes of 16 and 27 nm were synthesized through decomposition of iron (III) oleate under high temperature conditions and functionalized with a cationic lipidoid C12-200. Magnetic NC demonstrated good MR-contrasting properties. Biodistribution of LNP was studied in vivo in BALB/c mice using the MR scanner. Additionally, liver sections obtained from the mice were subjected to histological examination. Nanoparticles of smaller size did not have a cytotoxic effect on HepG2 and Huh7 cell lines, whereas for larger NC, IC50 was 21.5 mu g/ml and 126 mu g/ml for HepG2 and Huh7 cells, respectively. Smaller particles tended to accumulate in hepatocytes. Bigger NC mainly accumulated in the spleen but also ended up in liver macrophages. This fact can be explained by a bigger hydrodynamic size of nanoparticles with a bigger magnetic core. Particles with smaller cores are a more effective platform for the delivery of antisense drugs to hepatocytes.
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Key words
magnetic nanoparticles,MRI,lipids,targeted delivery
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