A1F5C5 is a core fluorinated ionizable lipid that forms the basis of the F5-LNP platform. Its key biological functions are multifaceted. Primarily, it enables efficient, targeted mRNA delivery in vivo. Following intravenous administration, F5-LNPs exhibit a strong tropism for the spleen and tumor sites, successfully transfecting over 70% of splenic macrophages and more than 20% of tumor-infiltrating macrophages. This allows for in situ cell engineering. Beyond delivery, A1F5C5 possesses intrinsic immunostimulatory activity. It promotes the maturation and activation of antigen-presenting cells (e.g., upregulating CD80/86 on dendritic cells) and enriches immune-related pathways like "cytokine-cytokine receptor interaction." Mechanistically, its unique 5-fluorine (F5) configuration confers superior membrane fusion capability, which is critical for efficient endosomal escape and cytosolic mRNA release. Therapeutically, when loaded with CAR mRNA, it serves as a platform for in vivo generation of CAR-macrophages (CAR-M). These CAR-M cells phagocytose tumors, reprogram the tumor microenvironment by shifting macrophages to an M1 phenotype, and activate CD8+ T cells. Notably, this approach synergizes powerfully with anti-PD-L1 therapy, achieving complete tumor regression in preclinical models.
