Pre-eclampsia is a placental insufficiency disorder that affects 3–5% of all pregnancies and is a leading cause of maternal and fetal morbidity worldwide. The pathogenesis of pre-eclampsia is characterized by broad placental dysfunction including poor perfusion, hypoxia, oxidative stress, and abnormal secretion of anti-angiogenic factors. No therapeutic has been clinically approved to slow or stop pre-eclampsia progression; rather, treatment plans focus on symptom management via antihypertensive and anticonvulsant medications. To develop a therapeutic that addresses the underlying placental dysfunction associated with pre-eclampsia, we sought to engineer a lipid nanoparticle (LNP) platform that facilitates delivery of pro-angiogenic vascular endothelial growth factor (VEGF) mRNA to the placenta. To this end, we first review recent literature that describes the design of therapeutic nanoparticle and biomaterial systems to deliver drugs for the treatment of conditions in non-pregnant and pregnant women (Chapter 1). We discuss the biological barriers, delivery challenges, and microenvironments unique to the female body that must be considered in the design of delivery technologies for women’s health applications. We then design a small library of LNP formulations with distinct ionizable lipid structures and demonstrate proof-of-concept in vivo mRNA LNP delivery to the placenta in pregnant mice (Chapter 2). To increase interdisciplinary work at the interface of nanomedicine, gene modulation, and reproductive health, we report detailed protocols for flow cytometric analysis of the murine placenta (Chapter 3) and the preparation of placenta-tropic mRNA LNPs (Chapter 4). Finally, we demonstrate the application of high-throughput in vivo screening to identify placenta-tropic LNPs from a large library of ~100 formulations with unique ionizable lipids and excipient compositions (Chapter 5). We propose a protein-adsorption-based endogenous targeting mechanism that enables LNP delivery to the placenta upon systemic administration. We show that this placenta-tropic VEGF mRNA LNP technology resolves maternal hypertension, placental dysfunction, and fetal growth restriction in both inflammation- and hypoxia-induced models of pre-eclampsia. In sum, we demonstrate the potential of this LNP platform for mRNA delivery to the placenta to treat pre-eclampsia and other placental disorders during pregnancy.