Abstract
SM-102 (1-octylnonyl 8-[(2-hydroxyethyl)[6-oxo-6-(undecyloxy)hexyl]amino]-octanoate) is an amino cationic lipid that has been tailored for the formation of lipid nanoparticles and it is one of the essential ingredients present in the ModernaTM COVID-19 vaccine. However, to what extent it may modify varying types of plasmalemmal ionic currents remains largely uncertain. In this study, we investigate the effects of SM-102 on ionic currents either in two types of endocrine cells (e.g., rat pituitary tumor (GH3) cells and mouse Leydig tumor (MA-10) cells) or in microglial (BV2) cells. Hyperpolarization-activated K+ currents in these cells bathed in high-K+, Ca2+-free extracellular solution were examined to assess the effects of SM-102 on the amplitude and hysteresis of the erg-mediated K+ current (IK(erg)). The SM-102 addition was effective at blocking IK(erg) in a concentration-dependent fashion with a half-maximal concentration (IC50) of 108 μM, a value which is similar to the KD value (i.e., 134 μM) required for its accentuation of deactivation time constant of the current. The hysteretic strength of IK(erg) in response to the long-lasting isosceles-triangular ramp pulse was effectively decreased in the presence of SM-102. Cell exposure to TurboFectinTM 8.0 (0.1%, v/v), a transfection reagent, was able to inhibit hyperpolarization-activated IK(erg) effectively with an increase in the deactivation time course of the current. Additionally, in GH3 cells dialyzed with spermine (30 μM), the IK(erg) amplitude progressively decreased; moreover, a further bath application of SM-102 (100 μM) or TurboFectin (0.1%) diminished the current magnitude further. In MA-10 Leydig cells, the IK(erg) was also blocked by the presence of SM-102 or TurboFectin. The IC50 value for SM-102-induced inhibition of IK(erg) in MA-10 cells was 98 μM. In BV2 microglial cells, the amplitude of the inwardly rectifying K+ current was inhibited by SM-102. Taken together, the presence of SM-102 concentration-dependently inhibited IK(erg) in endocrine cells (e.g., GH3 or MA-10 cells), and such action may contribute to their functional activities, assuming that similar in vivo findings exist.
Highlights
To make stock solution keep at −20 ◦ C, SM-102 was dissolved in chloroform, spermine in water and glyceryl nonivamide (GLNVA) in dimethyl sulfoxide (DMSO), while TurboFectinTM was in 80% ethanol solution
Summary bar graph showing effect of SM-102, intracellular dialysis with spermine, shows the voltage protocol used. (B) Summary bar graph showing effect of SM-102, intra or chlorotoxin on IK(IR) amplitude activated by ramp pulse
Chlorotoxin on IK(IR) amplitude activated by ramp pulse
Summary
8-[(2-hydroxyethyl)[6-oxo-6-(undecyloxy)hexyl]amino]-octanoate) is a synthetic and ionizable amino lipid that has been widely used in combination with other lipids in the formation of lipid nanoparticles [1,2]. The administration of luciferase mRNA in SM102-containing lipid nanoparticles was previously reported to induce hepatic luciferase expression in mice [3]. Formulations containing SM-102 have been noticeably used in Biomedicines 2021, 9, 1367. Biomedicines 2021, 9, 1367 the development of lipid nanoparticles for the delivery of mRNA-based vaccines [2,4,5], since such an efficient transfection procedure, based on compacted lipopolyamine-coated plasmids, has been developed [6]. SM-102 is known to be one of the ingredients in the ModernaTM COVID-19 vaccine (https://www.fda.gov/media/144638/download)
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