4-O10b1 is an ionizable cationic lipid (pKa = 5.148) that has been used in the generation of lipid nanoparticles (LNPs) for the delivery of siRNA in vitro and in vivo.1 LNPs containing 4-O10b1, conjugated to an antibody targeting the mouse macrophage marker F4/80 (anti-F4/80), and encapsulating siRNA targeting the mRNA encoding TGF-β-activated kinase 1 (Tak1) inhibit poly(I:C)-induced production of IL-1β, IL-6, and TNF-α in RAW 264.7 macrophages. In vivo, intranasal administration of these LNPs decreases lung injury and reduces total protein levels and myeloperoxidase (Mpo) activity in bronchoalveolar lavage fluid (BALF) in a mouse model of influenza A-induced pneumonia.
References:
[1]. Zhao, G., Xue, L., Geisler, H.C., et al.Precision treatment of viral pneumonia through macrophage-targeted lipid nanoparticle deliveryProc. Natl. Acad. Sci. USA121(7)e2314747121(2024).