CDL9 is an original cyclic disulfide lipid first designed, synthesized, and functionally validated in the study "In Vivo Demonstration of Enhanced mRNA Delivery by Cyclic Disulfide-Containing Lipid Nanoparticles for Facilitating Endosomal Escape" published in RSC Medicinal Chemistry (DOI: 10.1039/D5MD00084J).Its molecular architecture—featuring a C18:2 di-unsaturated alkyl chain linked to a tertiary amine headgroup modified with an α-lipoic acid-derived cyclic disulfide unit—was explicitly detailed in the paper's lipid library. Experimental data from this study demonstrated CDL9’s capacity to boost mRNA delivery efficiency by 6-fold in vitro and 5-fold in vivo when integrated into SM102-based LNPs, leveraging thiol-disulfide exchange for enhanced endosomal escape.
