CL4H6, a pH-sensitive cationic lipid, serves as the primary constituent of lipid nanoparticles (LNPs). These LNPs are instrumental in targeting and delivering siRNA, leading to a potent gene-silencing response [1] [2].

CL4H6 exhibits specialized targeting of hepatocytes and facilitates endosomal escape, enabling the safe and efficient delivery of myocardin-related transcription factor/serum response factor (MRTF/SRF)-B siRNA into human conjunctival fibroblasts [2].

The optimized siRNA-loaded CL4H6-LNPs selectively and efficiently target and inhibit gene expression in tumor-associated macrophages (TAMs) within a human tumor xenograft model in nude mice, demonstrating potent gene silencing activity. This anti-tumor effect is achieved by silencing STAT3 and HIF-1α genes, leading to an enhanced infiltration of macrophages (CD11b+ cells) into the tumor microenvironment (TME) and a likely increase in M1 macrophage (CD169+ cells) levels. Additionally, the treatment counteracts the pro-tumoral functions of TAMs, notably angiogenesis and tumor cell activation, as indicated by a reduction in specific gene expressions at the mRNA level [1].