# Engineering of Polymeric Particles for Fetal Therapy

> **NIH NIH R01** · YALE UNIVERSITY · 2023 · $431,757

## Abstract

PROJECT SUMMARY/ABSTRACT
Particle-based fetal therapy is a promising approach to address organ damage caused by structural diseases in
utero. By prenatal imaging, structural diseases can be diagnosed and imaging features can predict the severity
of outcome. Fetal surgery has demonstrated improved outcomes (but not cures) for structural diseases such as
congenital diaphragmatic hernia (CDH), where lung growth is impaired and spina bifida (MMC) where the
unprotected spinal cord is damaged. The challenges with fetal surgery are the complexity and invasive nature of
these procedures and the limit to how early in pregnancy these techniques can be applied. In most cases, earlier
treatment results in shortened duration of organ damage and longer duration of normal organ growth and
development. We have generated data that nanoparticles (NPs) carrying epigenetic therapy in the form of
specific microRNAs changes various downstream targets and improves the growth of lung in a rat of CDH. This
approach can be delivered safely through a needle very early in pregnancy by clinical techniques that carry a
very low rate of fetal demise (amniocentesis and fetal blood transfusion). To improve on our success in these
animal models, we will engineer particles for two modes of delivery: 1) systemic/intravenous (IV) to reach internal
organs (lung) and 2) intra-amniotic (IA) to reach tissues sites that are in contact with the amniotic fluid (such as
the lung epithelial surface). In aim 1, we will test and improve particle behavior (stability and controlled protein
binding) in human fetal blood to improve IV delivery. We will then use optimized particles to deliver epigenetic
therapy to improve lung morphology in the rat model of CDH. In aim 2, we will test and improve particle behavior
and stability in rat, lamb and human amniotic fluid to improve IA delivery. We will use particles carrying epigenetic
therapy to treat a rat model CDH. Finally, with an eye on translation, in aim 3, we will test the distribution of
particles in lamb after IV or IA administration to lung and other tissues. This project takes advantage of the
synergistic expertise (biomedical engineering and fetal therapy) of the two principal investigators who have
already worked together for several years. Successful completion of our aims will establish principles with broad
implications for fetal therapy, would inform strategies to improve outcomes for children afflicted with congenital
diseases. Our strategies—which aim for clinical translation—could lead to a paradigm-changing “off-the-shelf”
therapy for structural diseases that, due to their simplicity, could be offered at many hospitals.

## Key facts

- **NIH application ID:** 10586282
- **Project number:** 1R01EB032791-01A1
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** W. Mark Saltzman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $431,757
- **Award type:** 1
- **Project period:** 2023-05-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10586282

## Citation

> US National Institutes of Health, RePORTER application 10586282, Engineering of Polymeric Particles for Fetal Therapy (1R01EB032791-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10586282. Licensed CC0.

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