Disulfide bond-modified ionizable lipids for co-delivery of siRNA and carbon dots in the treatment of acute liver injury

Acute liver injury (ALI) is a severe clinical condition characterized by excessive oxidative stress and inflammatory responses, for which effective targeted therapeutic strategies remain limited. In this study, a redox-responsive ionizable lipid (Lipid S) was designed by incorporating a disulfide bond into its hydrophobic tail. Under reductive conditions, cleavage of the disulfide bond triggered rapid disassembly of the lipid nanoparticles (LNPs), enabling controlled cargo release. Using Lipid S, a nanoplatform (CD-siL@LNP-S) was established by loading small interfering RNA against interleukin-11 receptor alpha-1 (siIL11ra1) onto carbon dots (CDs) and encapsulating the resulting complex within lipid nanoparticles (LNPs). CD-siL@LNP-S exhibited stable physicochemical properties, efficiently silenced IL11ra1 expression, and reduced reactive oxygen species (ROS) production without inducing cytotoxicity. In an acetaminophen-induced ALI mouse model, the formulation preferentially accumulated in the liver and was efficiently taken up by hepatocytes, resulting in significant attenuation of oxidative stress, inflammation, and tissue injury while maintaining good systemic safety. Overall, Lipid S provides a simple and effective strategy for redox-responsive nucleic acid delivery, and CD-siL@LNP-S represents a promising therapeutic approach for oxidative stress-related liver diseases and other conditions with reductive intracellular environments.

Abstract from PubMed (PMID 42933516). This entry was added automatically by our daily literature monitor because it matches the topics we follow; read the full paper at the original source.