O. Taratula, A. Moses, L. Kadam, O. Taratula, L. Myatt, M.K. Baldwin
Oregon State University,
Keywords: placenta visualization, ectopic pregnancy, nanoparticles, photoacoustic imaging, photo-hyperthermia
Summary:Ectopic pregnancy (EP), which is an abnormal pregnancy implantation outside of the uterus, can cause internal bleeding if it is not promptly diagnosed and treated. EP remains the leading cause of maternity-related death during the first trimester of pregnancy, and early diagnosis is crucial for determining appropriate management strategies. In clinic today, EP diagnosis is definitely confirmed by ultrasound visualization of gestational sac implantation other than the ideal intrauterine location. However, ultrasound-confirmed diagnosis is challenging in the early stages, and dependent on body morphology and gestational duration. Thus, the diagnosis of EP with ultrasound could be erroneous in ~40% of cases, and subsequent chemotherapy (methotrexate-based) treatment (the most common treatment of EP without unstable bleeding) can lead to failed intrauterine pregnancy or live-born infants with developmental abnormalities. We developed photo-responsive near-infrared (NIR) nanoparticles (NIR-NP) that after systemically administration could be employed as photoacoustic imaging contrast agents to locate the developing placenta, and for subsequent photo-thermal elimination of the implantation sites when subjected to photo-hyperthermia. These nanoparticles preferentially accumulate in the developing murine placenta within 24 h following intravenous delivery, and enable visualization of implantation sites at various gestational stages as confirmed via fluorescence and photoacoustic imaging. These nanoparticles do not traverse the placental barrier to the fetus or impact fetal development. Besides, excitation of nanoparticles localized in specific placentas with focused NIR light generates heat (>43 °C) sufficient for disruption of placental function, resulting in the demise of targeted fetuses with no effect on adjacent fetuses. This novel approach would enable diagnostic confirmation of EP when current imaging strategies are unsuccessful, and elimination of EP could subsequently be achieved using the same nano-agent to generate localized hyperthermia resulting in targeted placental impairment.