Drug-resistant lung cancer was killed with 50 times less paclitaxel through an exosome delivery system. This research, done in cancer cell lines and mouse models, was published in Nanomedicine: Nanotechnology, Biology, and Medicine (doi:10.1016/j.nano.2015.10.012).
The exosomes used in this work are tiny spheres of cell membrane harvested from white blood cells, and they have gained recent attention as natural nanoparticles to deliver drugs. Because they are made from the same material as cell membranes, they protect the drug from being destroyed by the body’s own defenses and deliver the entire drug payload to the tumor. Exosomes overcome one of the most challenging issues with using plastics-based nanoparticle drug-delivery systems: they are not seen as foreign by a patient’s body.
“That means we can use 50 times less of the drug and still get the same results,” said Elena Batrakova, PhD, an associate professor in the Eshelman School of Pharmacy of the University of North Carolina at Chapel Hill, and corresponding author of the study. “That matters because we may eventually be able to treat patients with smaller and more accurate doses of powerful chemotherapy drugs resulting in more effective treatment with fewer and milder side effects.”
Batrokova explained that exosomes are engineered by nature to be the perfect drug delivery vehicles. Her research team extracted exosomes from mouse white blood cells and loaded them with paclitaxel.
Paclitaxel is used as first- and second-line treatments for breast, lung, and pancreatic cancers. Its serious side effects include hair loss, muscle and joint pain, and diarrhea. It can also put patients at greater risk of serious infection. Improving drug delivery could mean less drug is needed thereby reducing side effects.
The exosomes from mouse white blood cells were loaded with paclitaxel, dubbed exoPXT, and then tested against multiple-drug resistant cancer cells that were grown in petri dishes. The exoPXT needed was 50x less than the current formulations of the drug to achieve the same cancer-killing effect.
Further experiments in mouse models of drug-resistant lung cancer found that the exoPXT with dye added was thorough in seeking out and marking cancer cells, indicating that exoPXT could also be used as a diagnostic.
“Accurately mapping the extent of tumors in the lungs is one of the biggest challenges in treating lung cancer patients,” said Batrakova. “Our results show how powerful exosomes can be used as both a therapeutic and a diagnostic.”