Summary/Abstract
Ectopic pregnancy is the leading cause of maternity-related death during the first trimester of pregnancy.
Approximately 98 % of ectopic implantations occur in the fallopian tube and, in the event of tubal rupture, prompt
treatment is critical to avoid hemorrhage and maternal death. Ectopic pregnancies account for about one in every
50 pregnancies (120,000 per year) in the United States. Current ultrasonography procedures misdiagnose
ectopic pregnancy in up to 40% of cases, while methotrexate treatment for confirmed EP has a failure rate of
more than 10%. During the time prior to ultrasonographic visualization, the pregnancy biomarker human
chorionic gonadotropin (hCG) is used to evaluate growth but is a poor measure of the implantation site. This
project aims to establish an imaging modality for localization of the early placenta utilizing nanoparticles targeting
the trophoblast layer of the placenta. Contrast-enhanced imaging modalities (e.g., MRI) can substantially
improve ectopic pregnancy detection. However, the use of conventional contrast agents, including gadolinium-
based MRI contrast agents, is discouraged as low molecular weight compounds cross the placenta and can
incur fetal toxicity in viable pregnancies. To address this challenge, a biocompatible polymeric nanoplatform will
be utilized that accumulates specifically in placental tissue, but not the fetus, after intravenous injection. This
nanoplatform will be loaded with newly developed magnetic nanoparticles that are highly efficient MRI contrast
agents, and placenta accumulation/detection/visualization will be assessed in placenta cells and small animal
models. Furthermore, the ability to impair the developing placenta, and thus terminate ectopic pregnancy, will
be demonstrated by magnetic hyperthermia mediated by trophoblast-targeted nanoparticles. The premise of this
proposal is that specifically designed nanoparticles can detect early placentation, and subsequent magnetic
hyperthermia can provide a non-invasive option to treat ectopic pregnancy. To advance the proposed approach
for ectopic pregnancy management, our multidisciplinary team of investigators with complementary expertise in
nanomedicine, magnetic hyperthermia, and clinical placenta research proposes, in Aim 1, to evaluate the
biodistribution profile and placenta uptake of the developed nanoparticles (non-targeted and trophoblast-
targeted) in human/macaque placental cells and in mice. In Aim 2, the MRI imaging efficiency and short- and
long-term toxicity of the placenta-targeted nanoparticles will be evaluated in pregnant mice. In Aim 3, the safety
and therapeutic efficacy of magnetic hyperthermia mediated by our magnetic nanoparticles will be accessed for
simulated treatment of human ectopic pregnancy in mice and non-human primates, aiming to demonstrate a
novel, effective and non-invasive approach for ectopic pregnancy management.
