Placental-Targeted Theranostic Nanodroplets to Enhance Imaging and Therapeutic Delivery in Preeclampsia - Project Summary/ Abstract Preeclampsia is a leading cause of preventable maternal and fetal morbidity, yet no current therapy directly targets the placenta, the source of the disease. Existing treatments manage maternal symptoms but cannot restore placental oxygenation or vascular function, and they risk harmful fetal exposure. This F31 project addresses a critical gap in maternal–fetal medicine by developing the first placenta-targeted, image-guided theranostic platform capable of localized drug delivery with real-time evaluation of therapeutic response. The long-term goal is to advance precision treatments for pregnancy complications and prepare the applicant for an independent research career in maternal–fetal imaging and therapeutics. The proposed approach uses αvβ3- targeted perfluorocarbon nanodroplets (PFCnDs) co-loaded with LNS8801, a GPER agonist that improves vasodilation and trophoblast function, and bornite, a NIR-II photoacoustic chromophore that enables deep-tissue imaging and laser-triggered drug release. Aim 1 will optimize formulation, vaporization, drug-release kinetics, pharmacokinetics, and placental targeting using NanoSight characterization, spectral photoacoustic imaging, contrast-enhanced ultrasound, and in vitro trophoblast binding studies. Aim 2 will evaluate longitudinal therapeutic efficacy and safety in preeclampsia-relevant rat models by assessing placental oxygenation, perfusion, vascular remodeling, maternal blood pressure and cardiac function, fetal outcomes, and maternal–fetal drug distribution. The central hypothesis is that targeted, image-guided nanodroplet therapy will improve placental function and maternal cardiovascular health while minimizing fetal exposure. The fellowship provides structured training in biomedical optics, acoustics, nanomedicine, cardiovascular physiology, statistical analysis, and scientific communication through weekly mentoring with Dr. Bayer and co-mentoring with Dr. Lindsey. The Bayer Functional Imaging Laboratory and Lindsey cardiovascular biology group offer a uniquely complementary environment with advanced imaging systems, interdisciplinary expertise, and a strong record of training physician–scientists and biomedical engineers. Completion of this project will create the first integrated system that unites placental-targeted therapy with real-time ultrasound and photoacoustic imaging, opening new pathways for diagnosing, treating, and tracking preeclampsia.
