Researchers develop a new type of light-sensitive nanoparticle to help identify ectopic pregnancy

Hexbyte Glen Cove

Nanomedicine for treating ectopic pregnancy. Credit: Provided by Olena Taratula, OSU

Oregon State University scientists have produced a proof of concept for a new and better way of caring for women facing the life-threatening situation of ectopic pregnancy, which occurs when a fertilized egg implants somewhere other than the lining of the uterus.

Olena Taratula of the OSU College of Pharmacy and Leslie Myatt of Oregon Health & Science University led a team of researchers that used pregnant mice to develop a novel nanomedicine technique for diagnosing and ending ectopic pregnancies, which are non-viable and the leading cause of maternal death in the first trimester.

Findings were published in the journal Small.

The study is important because 2% of all pregnancies in the United States, and between 1% and 2% worldwide, are ectopic, the authors note. In the U.S. alone that translates to approximately 100,000 ectopic pregnancies annually.

About 98% of ectopic implantations happen in the , putting women at risk of hemorrhage and death. Complicating matters are a high misdiagnosis frequency—ultrasound yields an incorrect diagnosis 40% of the time—combined with a 10% failure rate of the primary drug, methotrexate, used to end an .

Roughly 70 women in the U.S. die each year from ectopic pregnancies, which are responsible for 10% of all -related deaths. Women who survive often struggle with a range of issues resulting from diagnosis and treatment, Taratula said.

“Current strategies include attempted diagnosis with transvaginal ultrasound, treatment with methotrexate, and surgery if necessary,” she said. “The strategies are associated with the risk of tubal rupture, reduced fertility and increased risk of another ectopic pregnancy—a woman who has had one ectopic pregnancy is 10% more likely to have a second one.”

And even when methotrexate—a drug that ends ectopic pregnancy by causing embryonic cells to stop dividing—is effective, it comes with a range of potential side effects, Taratula said: nausea, vomiting, diarrhea, elevated liver enzymes, kidney damage and lung disease.

To meet the challenges associated with diagnosing and treating ectopic pregnancies, Olena Taratula and Oleh Taratula of the OSU College of Pharmacy, as well as Myatt and Maureen Baldwin of OHSU, spearheaded a collaboration that developed a new type of light-sensitive nanoparticle. Nanoparticles are tiny pieces of matter, as small as one-billionth of a meter.

Administered intravenously, the new nanoparticles accumulate in the placenta, which nourishes and maintains the fetus through the umbilical cord. In a healthy pregnancy, the placenta forms inside the uterus, and in an ectopic pregnancy, it does not.

“Effective detection of the growing placenta would drastically improve the accurate and timely identification of ectopic pregnancy,” Olena Taratula said.

Once the nanoparticles are concentrated in the placenta, the organ can be seen through fluorescent and photoacoustic imaging, and it quickly becomes clear whether the placenta is where it’s supposed to be. If it is, the patient would know she did not have an ectopic pregnancy, and the embryo is unaffected by the particles as they do not cross the placental barrier.

If the placenta is in a or other incorrect location, the pregnancy could be ended by exposure to near-infrared light, which causes the nanoparticles to rise in temperature above 43 degrees Celsius and irreparably disrupt placental function via heat.

“Our main goal in this study was to evaluate our nanoparticle’s ability to identify and visualize the developing placenta and demonstrate its photothermal capabilities,” Taratula said. “Our experimental results are promising, and the next step is to validate it in other animal models to further advance the application of this technology.”

More information:
Abraham S. Moses et al, Nano‐Theranostic Modality for Visualization of the Placenta and Photo‐Hyperthermia for Potential Management of Ectopic Pregnancy, Small (2022). DOI: 10.1002/smll.202202343

Journal information:
Small


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Coulomb explosion imaging of iodopyridine (artists view). Credit: Goethe University Frankfurt am Main

Exploding a photo subject in order to take its picture? An international research team at the European XFEL, the world’s largest X-ray laser, applied this “extreme” method to take pictures of complex molecules. The scientists used the ultra-bright X-ray flashes generated by the facility to take snapshots of gas-phase iodopyridine molecules at atomic resolution. The X-ray laser caused the molecules to explode, and the image was reconstructed from the pieces. “Thanks to the European XFEL’s extremely intense and particularly short X-ray pulses, we were able to produce an image of unprecedented clarity for this method and the size of the molecule,” reports Rebecca Boll from the European XFEL, principal investigator of the experiment and one of the two first authors of the publication in the scientific journal Nature Physics in which the team describes their results. Such clear images of complex molecules have not been possible using this experimental technique until now.

The images are an important step towards recording molecular movies, which researchers hope to use in the future to observe details of biochemical and chemical reactions or physical changes at high resolution. Such films are expected to stimulate developments in various fields of research. “The method we use is particularly promising for investigating photochemical processes,” explains Till Jahnke from the European XFEL and the Goethe University Frankfurt, who is a member of the core team conducting the study. Such processes in which chemical reactions are triggered by light are of great importance both in the laboratory and in nature, for example in photosynthesis and in visual processes in the eye. “The development of molecular movies is fundamental research,” Jahnke explains, hoping that “the knowledge gained from them could help us to better understand such processes in the future and develop new ideas for medicine, sustainable energy production and materials research.”

In the method known as Coulomb explosion imaging, a high-intensity and ultra-short X-ray laser pulse knocks a large number of electrons out of the molecule. Due to the strong electrostatic repulsion between the remaining, positively charged atoms, the molecule explodes within a few femtoseconds—a millionth of a billionth of a second. The individual ionized fragments then fly apart and are registered by a detector.

“Up to now, Coulomb explosion imaging was limited to small molecules consisting of no more than five atoms,” explains Julia Schäfer from the Center for Free-Electron Laser Science (CFEL) at DESY, the other first author of the study. “With our work, we have broken this limit for this method.” Iodopyridine (C5H4IN) consists of eleven atoms.

The film studio for the explosive molecule images is the SQS (Small Quantum Systems) instrument at the European XFEL. A COLTRIMS reaction microscope (REMI) developed especially for these types of investigations applies electric fields to direct the charged fragments onto a detector. The location and time of impact of the fragments are determined and then used to reconstruct their momentum—the product of mass and velocity—with which the ions hit the detector. “This information can be used to obtain details about the molecule, and with the help of models, we can reconstruct the course of reactions and processes involved,” says DESY researcher Robin Santra, who led the theoretical part of the work.

Coulomb explosion imaging is particularly suitable for tracking very light atoms such as hydrogen in . The technique enables detailed investigations of individual molecules in the gas phase, and is therefore a complementary method for producing molecular movies, alongside those being developed for liquids and solids at other European XFEL instruments.

“We want to understand fundamental photochemical processes in detail. In the gas phase, there is no interference from other molecules or the environment. We can therefore use our technique to study individual, isolated molecules,” says Jahnke. Boll adds that they “are working on investigating as the next step, so that individual images can be combined into a real molecular movie, and have already conducted the first of these experiments.”



More information:
Rebecca Boll, X-ray multiphoton-induced Coulomb explosion images complex single molecules, Nature Physics (2022). DOI: 10.1038/s41567-022-01507-0. www.nature.com/articles/s41567-022-01507-0

Citation:
Molecule snapshot by explosion (20

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