Researchers have identified a promising new approach to treat pre-eclampsia, a pregnancy complication that affects 3-5% of pregnancies worldwide and is a leading cause of maternal and fetal death. The research team, led by NIH Director’s High-Risk, High-Reward New Innovator Award recipient Michael Mitchell, Ph.D., at the University of Pennsylvania, discovered a specialized nanoparticle that could deliver therapeutic agents directly to the placenta and slow progression of pre-eclampsia in mice.

Pre-eclampsia is a complicated placental disorder characterized by maternal high blood pressure. In pre-eclampsia, blood flow around the placenta is abnormal, affecting blood flow to the fetus and increasing blood pressure in the pregnant mother. This can lead to fetal growth restrictions and possible preterm birth. Currently, there is no clinically proven treatment to slow pre-eclampsia progression, and often the only option to resolve the disease is delivery of the fetus. 

Past research to treat pre-eclampsia has sought the use of nucleic acids, small molecules that carry instructions, to silence the signaling molecules that disrupt blood flow in the placenta. However, using this kind of approach to treat pre-eclampsia requires a way to deliver the therapeutic nucleic acid directly to the placenta and until now, no targeting strategy has shown meaningful impact on disease progression. 

Lipid nanoparticles (LNPs) are emerging as powerful biomedical tools for delivering nucleic acid-based therapies. They are nanoscopic particles that can reach target tissues precisely and with less unwanted side effects and have been effective in treating other diseases including a heritable liver disease. Dr. Mitchell and his team are adapting LNPs to target the placenta to deliver therapeutic agents that treat pre-eclampsia. The group screened 98 different LNP formulations to find any that might have an affinity for the placenta. One version, LNP-55, showed great potential. 

In mouse experiments, LNP-55 delivered almost 200-times more experimental compound to the placenta compared to the industry standard, showing that LNP-55 strongly targets the placenta. Further, when coupled with high blood pressure characteristic of pre-eclampsia, even more compound was delivered to the placenta using LNP-55.

The team paired LNP-55 with a pre-eclampsia therapeutic nucleic acid and found a single injection of LNP-55 with the therapeutic agent permanently alleviated high blood pressure in the pre-eclamptic pregnant mouse all the way through the end of pregnancy. 
Although additional research is needed before this formulation can be used in humans, LNP-55 holds strong potential to transform treatment of placental disorders like pre-eclampsia, offering hope for healthier pregnancies and reduced maternal mortality rates.

Swingle, K.L., Hamilton, A.G., Safford, H.C., Geisler, H.C., Thatte, A.S., Palanki, R., Murray, A.M., Han, E.L., Mukalel, A.J., Han, X., Joseph, R.A., Ghalsasi, A.A., Alameh, M., Weissman, D., Mitchell, M.J. Placenta-tropic VEGF mRNA lipid nanoparticles ameliorate murine pre-eclampsia. Nature. 637, 412-421 (2025).