A newly developed drug delivery system appears to be effective for treating a rare and aggressive type of cancer that impacts pregnant women and new mothers, and it may also be beneficial for other types of cancer.
A newly developed drug delivery system appears to be effective for treating a rare and aggressive type of cancer that impacts pregnant women and new mothers, and it may also be beneficial for other types of cancer.
Researchers, led by Olena Taratula, a specialist in nanomedicine at Oregon State University, have devised a method to ensure that the medication intended to fight this disease effectively reaches cancerous tumor cells while sparing healthy tissues.
The study focused on choriocarcinoma, which occurs at an incidence of about four cases per 100,000 pregnancies in the United States, and its findings were published in Small Science.
Choriocarcinoma typically originates in the uterus from cells that were part of the placenta. It may arise following a miscarriage, abortion, or ectopic pregnancy, where the fertilized egg implants outside the uterine lining.
This type of cancer can also develop after a molar pregnancy, where no embryo forms and abnormal growth of placental tissue occurs, or even following a full-term pregnancy.
Taratula and her team, which included OSU postdoctoral researcher Babak Mamnoon and Oregon Health & Science University physician Maureen Baldwin, created a specialized type of drug carrier, known as a polymersome, designed to target a specific protein found in choriocarcinoma cells.
Polymersomes are hollow spheres made from synthetic materials, resembling liposomes, which are lipid-based pockets present in all living cells. The specific protein of interest is the equilibrative nucleoside transporter 1, abbreviated as ENT-1, which plays a crucial role in various cellular activities, such as the synthesis of DNA and RNA.
ENT-1 is not only prevalent in choriocarcinoma cells but is also found in other vital organs like the brain, heart, and liver.
Under Mamnoon’s leadership, the research team conducted tests using mouse models that demonstrated that adding guanosine, a component of RNA, to the polymersome allowed for more efficient delivery of the chemotherapy drug methotrexate directly to the tumor cells.
“Since methotrexate is a primary treatment for choriocarcinoma, an important objective now is to improve its efficiency, including faster response times, while concurrently reducing side effects,” stated Taratula, an associate professor in the OSU College of Pharmacy.
Methotrexate, often referred to as MTX, is a common chemotherapy medication that disrupts cells’ utilization of folic acid, which is vital for DNA and RNA production. By inhibiting a key enzyme, MTX disrupts the rapid division of cancer cells.
Common signs of choriocarcinoma include pelvic pain and abnormal vaginal bleeding. The cancer can rapidly disseminate through the bloodstream to various organs, including bones, the gastrointestinal tract, breasts, kidneys, liver, lungs, lymph nodes, and even the brain.
“Since choriocarcinoma typically affects individuals who have recently been pregnant, they often have young families, which means we should make the diagnosis and treatment process quicker and more accessible,” said Baldwin, an obstetrician/gynecologist at OHSU.
Most cases are highly treatable, especially if diagnosed early, boasting a five-year survival rate of approximately 87%.
“However, standard applications of MTX lack tumor specificity and can lead to side effects like liver and kidney damage,” remarked Taratula. “That’s why we need a uniquely designed nanoplatform to ensure precise drug delivery and effective release directly into tumors.”
The mouse model studies showed that this method reduced tumor size by 95%, functioning nearly six times more effectively than non-targeted drug carriers. The result is more effective treatment along with reduced or less severe side effects, and with additional research, this strategy could potentially be adapted for other cancers, according to Taratula.
The study was funded by the OSU College of Pharmacy, the OHSU School of Medicine, the National Institutes of Health, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
Other collaborators included Ana Paula Mesquita Souza, Tetiana Korzun, K. Shitaljit Sharma, Oleh Taratula, Yoon Tae Goo, Prem Singh, Vladislav Grigoriev, and Aryan Lakhanpal from Oregon State University.
