EB-Lipid

Биологическая активность

EB-липид is an innovatively engineered ионизируемый липид designed to replace conventional PEG-липид in mRNA vaccine formulations. Its structure comprises three key components: an Evans Blue-derived headgroup with high affinity for albumin, a tetraethylene glycol linker that enhances colloidal stability, and dual oleate tails for anchoring into липид bilayers. This molecular design enables EB-липид to actively recruit endogenous albumin, forming an albumin-rich protein corona on the surface of липид nanoparticles (LNPs). Following intramuscular administration, these albumin-bound EB-LNPs are preferentially transported through lymphatic vessels rather than entering the bloodstream, thereby avoiding hepatic accumulation and associated hepatotoxicity risks.Experimental data demonstrate that EB-LNPs achieve significantly higher accumulation in lymph nodes, where they are efficiently internalized by dendritic cells via albumin рецептор-mediated endocytosis (e.g., gp60). This process enhances antigen presentation and activates robust клеточный and humoral immune responses. In both tumor models (B16-OVA and HPV-associated) and infectious disease models (H1N1 and SARS-CoV-2 Omicron), EB-LNP-based mRNA vaccines elicited мощный cytotoxic T-клетка activation and durable neutralizing антитело production at low doses. Unlike traditional PEG-LNPs, EB-LNPs show minimal liver distribution, reduced immunogenicity, and improved safety profiles after repeated administrations.By leveraging albumin’s natural trafficking pathway, EB-липид represents a transformative delivery platform that combines targeted lymph node delivery with enhanced biosafety, positioning it as a promising candidate for next-generation mRNA vaccines and therapeutics.