The chemotherapy drug paclitaxel is commonly used to treat breast, lung and pancreatic cancers, slowing their growth by preventing cancerous cells from replicating. But once administered the drug is attacked by the body's defenses, necessitating larger doses that result in complications such as joint pain, diarrhea and an impaired ability to fend off other infections. Researchers have now discovered a way to sneak the drug through to the tumor with its entire payload intact, a technique that could make for more effective cancer treatments with fewer side effects.
In investigating ways cancer drugs may be able to slip through the body's defenses, scientists at the University of North Carolina at Chapel Hill were experimenting with exosomes. Derived from the body's white blood cells, these tiny bubbles are made from the same material as cell membranes and help to protect against infection. The same researchers have had some promising results in using exosomes as a way to sneak drugs into the brain to treat neurological disorders.
"Exosomes are engineered by nature to be the perfect delivery vehicles," says Elena Batrakova, associate professor in the UNC Chapel Hill. "By using exosomes from white blood cells, we wrap the medicine in an invisibility cloak that hides it from the immune system. We don't know exactly how they do it, but the exosomes swarm the cancer cells, completely bypassing any drug resistance they may have and delivering their payload."
Putting the new technique to the test, the team used exosomes taken from mouse white blood cells, loaded them up with paclitaxel and put them to work against multiple-drug-resistant cancer cells in petri dishes. The team observed that they only need one fiftieth of the commonly used dosage of paclitaxel to have the same cancer-killing success.
"That means we can use 50 times less of the drug and still get the same results," says Batrakova. "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."
Further adding to the credentials of the treatment, which the researchers have dubbed exoPXT, is its potential to double as a diagnostics tool. Using the technique on mouse models of drug-resistant lung cancer, the team also added a dye to the exosomes, finding that they were effective in marking the cancer cells as they went about their business.
"Accurately mapping the extent of tumors in the lungs is one of the biggest challenges in treating lung-cancer patients," says Batrakova. "Our results show how powerful exosomes can be as both a therapeutic and a diagnostic."
The research was published in the journal Nanomedicine: Nanotechnology, Biology and Medicine.
Source: University of North Carolina
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