Tidal Lipid 40is an ionizable cationic lipid engineered to deliver RNA with high precision to immune cells like macrophages. Based on Tidal Therapeutics' patent US 20250205169A1, Its pH-responsive design shifts from a +8 mV charge at pH 5.5 (enabling endosomal escape) to near-neutral at pH 7.4 (reducing off -target binding), ensuring efficient intracellular release while maintaining blood stability. In lipid nanoparticles, Lipid 40 achieves 65% transfection efficiency in human macrophages—surpassing benchmarks like ALC-0315—and protects >95% of RNA payloads from degradation. Critically, it maintains particle integrity after freeze-thaw cycles with minimal size drift (<5 nm) and excels in in vivo targeting, driving potent gene expression in tumor-associated macrophages while avoiding liver/spleen accumulation. This combination of precision delivery, stability, and low toxicity makes it ideal for immunotherapies, such as reprogramming M2 macrophages to anti-tumor M1 states.
