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Fetus

Poster Session 3

(817) Trans-placental transport of a novel fluorescent lipid nanoparticle in a pre-clinical fetal therapy murine model

Wednesday, February 14, 2024
8:30 AM – 10:00 AM  
Location: Prince George's Exhibit Hall CDE, Lower Atrium Level
Objective: In utero therapies allow for prevention of irreversible fetal morbidity. While preferential transplacental delivery for fetal treatment is challenging, lipid nanoparticles (LNPs) offer an established safety profile, and lipoprotein-rich fetal blood provides a compatible environment. Since modifications in LNP composition allow for fetal tissue target specificity, we hypothesized that a specialized LNP delivery vehicle with near infrared (NIR) fluorescence detection would enable targeted fetal delivery which could be readily visualized in vivo after peripheral administration to a gravid mouse.

Study Design: DiR, a NIR fluorescent dye, and other lipids dissolved in EtOH were rapidly mixed with buffer and sonicated to form DiR LNPs at 6 mM lipid concentration. 1.7 mg/uL DiR LNPs were injected into the tail veins of e14.5 gravid mice (n=2). Images were obtained at 4 timepoints before removing the maternal uterus, liver, kidneys, and viscera for imaging. The fetuses and placentae were subsequently imaged as well.

Results: As anticipated, maternal in vivo images demonstrated strong fluorescent LNP signal in the liver at all timepoints (Fig1A). Initial faint LNP signal in the maternal uterus became concentrated in the distribution of the L uterine horn (Fig1B). Excitingly, the fluorescent LNP signal was observed in every placenta and fetus (Fig1C), and honed to the fetal liver. At high resolution, revealing there was preferential LNP signal in the fetal live over the other abdominal viscera (Fig1D).

Conclusion: These data show, for the first time, successful in vivo trans-placental LNP delivery to fetal mice via intravenous injection of a gravid mouse, with preferential uptake in the fetal liver. These findings are an exciting next step in the development of a novel, maternal peripherally delivered yet transplacental LNP delivery of cargo to the fetal liver for in utero fetal therapies.