200Oi10 is an ionizable lipidoid used in lipid nanoparticles (LNPs) for RNA delivery. Structurally, it features ester-conjugated cleavable lipid tails, enhancing biodegradability and reducing toxicity compared to non-cleavable analogs. Preclinical studies show that 200Oi10-based LNPs primarily accumulate in the liver (97.7%) after intravenous administration. However, intraperitoneal injection redirects biodistribution, achieving 46.4% pancreatic uptake, which can be further amplified by incorporating cationic lipids like DOTAP. This unique tropism enables pancreas-targeted mRNA delivery. 200Oi10's ester linkages promote rapid clearance, improving biocompatibility while maintaining siRNA/mRNA delivery efficiency. Its design exemplifies the use of degradable lipidoids to balance organ specificity, efficacy, and safety in RNA therapeutics.
