Q&A: Nanotechnology may offer better diagnosis, treatment of ectopic pregnancy
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Using a new technology, future clinicians may be able to more accurately diagnose and appropriately treat ectopic pregnancies than they would with traditional methods, according to data published in Small.
Leslie Myatt, PhD, FRCOG, a professor of OB/GYN at Oregon Health & Science University in Portland, and Olena R. Taratula, PhD, an associate professor at the Oregon State University College of Pharmacy in Corvallis, led a research team in developing and testing an investigational nanotechnology-based treatment for ectopic pregnancy.
“Too many people become seriously ill and even die because the best-available methods to detect and treat ectopic pregnancies simply aren’t good enough,” Myatt said in a press release. “I hope research like this will create better options for those who unfortunately experience an ectopic pregnancy.”
Healio spoke with Myatt to learn more about ectopic pregnancy and the potential the new technology holds for its treatment.
Healio: What is an ectopic pregnancy?
Myatt: An ectopic pregnancy occurs when the blastocyst — a cluster of cells made by a fertilized egg — implants outside the uterus, develops into the placenta and embryo and hence grows in the wrong place. The great majority of ectopic pregnancies are in the fallopian tube.
The placenta invades into nearby blood vessels to gain a blood supply and can cause internal bleeding. The placenta and fetus will grow, and this growth can cause the fallopian tube to rupture if not diagnosed and treated.
Symptoms include severe pain on one side of the abdomen and sometimes bleeding.
Ectopic pregnancies cannot result in a continuing pregnancy and must be treated to prevent significant illness, the potential for future infertility and even death.
Healio: Whom does it affect?
Myatt: Ectopic pregnancy affects between 1% to 2% of patients — up to 100,000 per annum in the United States. It is thought to be responsible for 10% of the 700 maternal deaths per annum in the U.S. Most deaths associated with ectopics occur in the first trimester.
Healio: Why is it difficult to detect and treat?
Myatt: The current technology (vaginal ultrasound) used to locate and diagnose ectopic pregnancy may miss a diagnosis in up to 40% of cases.
The current medical therapy is to administer the cancer drug methotrexate, which prevents multiplication of rapidly dividing cells (ie, the placenta and embryo). Methotrexate often causes side effects such as nausea, vomiting and renal and liver effects, and fails to end about 10% of ectopic pregnancies, which means a repeat treatment or perhaps surgery, which itself may affect future fertility. Advanced cases may require immediate surgery and can be associated with significant blood loss.
In the case of misdiagnosis of a normal pregnancy as ectopic, methotrexate use will cause demise of that normal pregnancy.
Healio: How does this technology work?
Myatt: We use very small (38 nm, which is 2,000 times smaller than the diameter of human hair) biocompatible nontoxic nanoparticles that contain a near-infrared photo-responsive molecule, silicon naphthalocyanine (SiNc). The nanoparticles will accumulate in highly vascularized tissues such as the placenta. The properties of the nanoparticle allow it to be then visualized using fluorescence or photoacoustic imaging.
Using the pregnant mouse as a proof-of-principle model, we have shown that after injection, the nanoparticles accumulate in the placenta and can be clearly seen either by fluorescence or by photoacoustic imaging.
Further, upon 10 minutes of targeted exposure to near-infrared light, the nanoparticles heat up sufficiently — to about 43°C (110°F) — to cause demise of the placental tissue and then loss of that targeted placenta and fetus. We call it in vivo photo-hyperthermia (PHT). The surrounding tissue is undamaged.
Importantly, the nanoparticle does not cross to the fetus. Hence, if it is administered to a pregnant individual and the pregnancy turns out to be normal and the PHT is therefore not used, then the pregnancy can be allowed to continue in the knowledge the nanoparticle has not reached the fetus.
Healio: What issues are there in implementing it in people?
Myatt: There are obviously safety issues that need to be answered before implementation in people. These include showing the particle has no off-target effects and does not accumulate in other tissues and cause side effects. We have to show there is no risk to subsequent fertility from this treatment.
If the nanoparticle is administered to someone where the pregnancy is found to be normal, we have to show the nanoparticle does not cause any deleterious effects to that ongoing pregnancy or to the mother or her offspring subsequently.
To address these issues, we are performing toxicity, future fertility and follow-up studies of treated mothers and offspring in mice. We are also planning to perform studies in a non-human primate, which has a physiology that closely resembles that of humans.
We are further refining the method to include specific targeting of the nanoparticle to the placenta by adding a targeting peptide to its surface. This should mean we need to use less of the nanoparticle and also lower the possibility of off-target effects in other tissues.
We are also planning to include methotrexate inside the nanoparticle itself to deliver it directly to the placenta and therefore use less methotrexate and avoid side effects.
Healio: When could this be available for use in people?
Myatt: We believe it will be several years before the treatment is available for use in humans.
References:
- Moses AS, et al. Small. 2022;doi:10.1002/smll.202202343.
- White F. Nanotechnology may better identify, treat ectopic pregnancy. https://news.ohsu.edu/2022/11/21/nanotechnology-may-better-identify-treat-ectopic-pregnancy. Published Nov. 21, 2022. Accessed Nov. 29, 2022.