January 14, 2016
For the first time, scientists at the University of North Carolina at Chapel Hill have packaged the cancer drug paclitaxel in exosomes — containers derived from a patient’s own immune system — to make it 50 times more potent against drug-resistant lung-cancer tumors.
Elena Batrakova, Ph.D., and her colleagues at the UNC Eshelman School of Pharmacy’s Center for Nanotechnology in Drug Delivery harvested tiny spheres called exosomes from macrophages, white blood cells that protect the body against infection. Exosomes carry chemical messages and are made of the same material as cell membranes. Diseases like cancer and AIDS propagate throughout the body by hijacking exosomes, but Batrakova is using them as a natural drug-delivery system. The exosomes can also deliver a dye that stains tumors and makes it easy to see how widespread the cancer is.
Like the synthetic nanoparticles currently being used to deliver many chemotherapeutic agents, exosomes have a natural ability to home in on tumors. Unlike those manmade particles, which are often seen as foreign objects and swept up by the immune system, exosomes derived from white blood cells are ignored by the patient’s natural defenses because they are part of them and are allowed to deliver their payload unimpeded. The team’s finding were published online in Nanomedicine: Nanotechnology, Biology and Medicine.
“Exosomes are engineered by nature to be the perfect delivery vehicles,” said Batrakova, who is an associate professor in the Division of Molecular Pharmaceutics. “By using exosomes from white blood cells, we wrap the medicine in an invisibility cloak that hides it from the immune system. While we don’t know exactly how they do it yet, the exosomes swarm the cancer cells, completely bypassing any drug resistance they may have and delivering their chemotherapy payload.”
Paclitaxel is a potent drug used in the U.S. as a first- and second-line treatment for breast, lung and pancreatic cancers. It can have serious and unpleasant side effects, such as hair loss, muscle and joint pain and diarrhea, and it can put patients at greater risk of serious infection.
In their experiment, Batrakova’s team extracted exosomes from mouse white blood cells and loaded them with paclitaxel. They then tested the treatment — which they call exoPXT — against multiple-drug-resistant cancer cells in petri dishes. The team saw that they needed 50 times less exoPXT to achieve the same cancer-killing effect as formulations of the drug currently being used, such as Taxol.
The researchers next tested the therapy in mouse models of drug-resistant lung cancer. They loaded the exosomes with a dye in order to track their progress through the lungs and found that the exosomes were thorough in seeking out and marking cancer cells, making them a surprisingly effective diagnostic tool in addition to being a powerful therapeutic, Batrakova said.
“We were very pleased to see how thoroughly the dye-carrying exosomes marked the cancerous cells in the lung tissue,” she said. “Accurately mapping the extent of tumors in the lungs is one of the biggest challenges in treating lung-cancer patients. Our results show how powerful exosomes can be as both a therapeutic and a diagnostic.”
Batrakova and her team at the pharmacy school have previously demonstrated success using the same technique in delivering therapies to treat Parkinson’s disease. Batrakova says her hope in developing exosome therapies for cancer is that patients can be treated with smaller and more accurate doses of powerful chemotherapy drugs resulting in more effective treatment with fewer and milder side effects.
Study Funding and Authors
Batrakova’s study was supported by the National Institutes of Health and the Carolina Partnership, a strategic partnership between the UNC Eshelman School of Pharmacy and the University Cancer Research Fund through the UNC Lineberger Comprehensive Cancer Center, as well as the Russian Federation Ministry of Education and Science.
Batrakova is the senior author of the study. The following are the addition authors:
- Myung Soo Kim, a graduate student in the Division of Molecular Pharmaceutics and the lead author
- Matthew Haney, a research technician in the CNDD
- Yuling Zhao, a research specialist in the CNDD
- Vivek Mahajan, Ph.D.
- Irina Deygen, Department of Chemical Enzymology, Faculty of Chemistry, M.V. Lomonosov Moscow State University
- Natalia Klyachko, Ph.D., Dr.Sci., an adjunct professor at the School, member of the CNDD and professor and deputy director of the Research and Education Center on Nanotechnology at Moscow State University
- Eli Inskoe, an undergraduate student at UNC
- Aleksandr Piroyan, Ph.D.
- Marina Sokolsky, Ph.D., research assistant professor in MOPH and director of the CNDD Nanoformulation Core Facility
- Onyi Okolie, a graduate student in MOPH
- Shawn Hingtgen, Ph.D., assistant professor in MOPH
- Alexander Kabanov, Ph.D., Dr. Sci., Howard and Mescal Ferguson Distinguished Professor and director of the CNDD