Using immune cells as carriers for nanoparticle-containing anti-cancer drugs may be a promising strategy to develop targeted therapies that affect tumor cells without damaging healthy cells.
Indeed, loading immune cells with nanoparticles containing Zelboraf (vemurafenib), an approved melanoma therapy, led to the targeted delivery of these nanoparticles into circulating melanoma cells, which effectively killed the cancer cells.
The study, “Immune Cell-Mediated Biodegradable Theranostic Nanoparticles for Melanoma Targeting and Drug Delivery,” was published in Small.
“The traditional way to deliver drugs to tumors is to put the drug inside some type of nanoparticle and inject those particles into the bloodstream,” Jian Yang, professor of biomedical engineering at Penn State, said in a press release. “Because the particles are so small, if they happen to reach the tumor site they have a chance of penetrating through the blood vessel wall because the vasculature of tumors is usually leaky.”
Researchers have come up with ways of improving the odds of those nanoparticles interacting with cancer cells by coating them with antibodies that recognize specific cancer proteins, but the effectiveness of these nanoparticles still relied on them actually reaching the tumor.
In an attempt to develop a more specific method of sending drugs to tumors, Yang and the immunologist Cheng Dong focused on using immune cells to deliver these loaded nanoparticles. Because immune cells are naturally attracted to the inflammatory signature of the tumor, chances were they could work as carriers for targeted anti-cancer therapies.
“I have 10 years of working in immunology and cancer,” Dong said. “Jian is more a biomaterials scientist. He knows how to make the nanoparticles biodegradable. He knows how to modify the particles with surface chemistry, to decorate them with peptides or antibodies. His material is naturally fluorescent, so you can track the particles at the same time they are delivering the drug, a process called theranostics that combines therapy and diagnostics.
“On the other hand, I study the cancer microenvironment, and I have discovered that the microenvironment of the tumor generates kinds of inflammatory signals similar to what would happen if you had an infection,” Dong said.
The researchers used a human leukemia cell line called THP-1 which is known to have affinity to cancer cells and other inflammatory cells. They then loaded them with nanoparticles containing Zelboraf.
The nanoparticles were biodegradable and bioluminescent, which allowed the team to follow their localization. Importantly, the immune cells were found to bind to melanoma cells, even when they were in conditions that mimicked the bloodstream, and that the nanoparticles could then be transferred into the melanoma cells, which led to their death.
Although these experiments were all done in culture dishes, the researchers now want to test whether these immune cells can also deliver the nanoparticles to tumors in distinct animal models and how that influences tumor growth and survival.
“This is the first study and is just to show that the technology works,” Dong said. “This study is not about curing melanoma. There are probably other ways to do that. We used melanoma cells to validate the approach.”