SM-102 is the only ionizable amino cationic lipid currently clinically approved for RNA therapeutics and can be used to synthesize lipid nanoparticles (LNPs). It shows potential in the development of LNPs for the delivery of mRNA-based vaccines.

METHODS: The effects of SM-102 on ionic currents in two endocrine cells, rat pituitary tumor (GH3) cells and mouse Leydig tumor (MA-10) cells, or microglial cells (BV2), were investigated. Hyperpolarization-activated K currents in these cells bathed in a high-K, Ca2+-free extracellular solution were examined to assess the effects of SM-102 on the amplitude and hysteresis of erg-mediated K currents (I+K(erg)). RESULTS The addition of SM-102 effectively blocked IK(erg) in a concentration-dependent manner with a half-peak concentration (IC50) of 108 μM, which was similar to the KD value required for its enhanced current inactivation time constant (i.e., 134 μM); in the presence of SM-102, exposure of cells to the transfection reagent TurboFectinTM 8.0 (0.1%, v/v) was able to effectively inhibit hyperpolarization-activated IK(erg) and increase the inactivation time course of the current; in addition, in GH3 cells dialyzed with spermine (30 μM), the amplitude of IK(erg) gradually decreased; further use of SM-102 (100 μM) or TurboFectin (0.1%) further reduced the current amplitude; in MA-10 Leydig cells, the IC50 value of SM-102-induced IK(erg) inhibition in MA-10 cells was 98 μM. In BV2 microglia, the amplitude of inwardly rectifying K currents is inhibited by SM-102.[3]