There are a number of research teams working on discovering new, safer ways to deliver cancer-fighting drugs to a tumor without causing damage to healthy cells. Others are researching different ways to boost the body’s own immune system so that it will attack cancer cells. Researchers at Penn State have combined the two approaches for the first time. They have conjugated specific cancer-fighting drugs with biodegradable polymer nanoparticles encapsulated into immune cells to create a targeted, smart system to attack specific types of cancers.
Jian Yang, professor of biomedical engineering at Penn State, explained that drugs are traditionally delivered to tumors by putting the drug inside some type of nanoparticle and then injecting those particles into the bloodstream. As the vasculature of tumors is usually leaky, the tiny particles have a chance of penetrating through the blood vessel wall when they reach the tumor site.
By coating the outside of the nanoparticles with antibodies or certain peptides or proteins, the chances of interacting with cancer cells is improved. The coating will lock onto the cancer cell when they make contact. This is however still a passive drug delivery technology. There is no chance of the particles binding and delivering the drug if they do not go to the tumor.
Cheng Dong, department head and professor of biomedical engineering, worked with Yang on this research. They wanted a method that is more active to target drugs to the cancer wherever it was located. They aim was to reach cancers circulating in the brain, or in the blood, or in any other organ of the body.
Dong has 10 years working experience in immunology and cancer, while Yang specializes in biomaterials. Yang knows how to modify the particles with surface chemistry to bedeck them with antibodies or peptides and how to make the nanoparticles biodegradable. As his material is naturally fluorescent, the particles can be tracked at the same time as they are delivering the drug. This process is called theranostics and it combines diagnostics and therapy.
Dong on the other hand, studies the cancer microenvironment. He has discovered that the microenvironment of a tumor produces inflammatory signals similar to those generated during an infection. Dong explained that immune cells are attracted to the tumor site naturally, as they have been built to respond to inflammatory signals. Immune cells will therefore make a perfect active delivery system for Yang’s nanoparticles. It is also likely that the same technology will be effective for tissue regeneration, as well as for infectious or other diseases.
Circulating melanoma cells were targeted by the two research groups in the first proof of their technology. The results were published in the current online issue of the journal Small, in a paper titled “Immune Cell-Mediated Biodegradable Theranostic Nanoparticles for Melanoma Targeting”. The researchers describe the use of a novel photoluminescent and biodegradable polymer (lactic acid) (BPLP-PLA) nanoparticle. The nanoparticle was loaded with melanoma specific drugs, while immune cells were used as the nanoparticle carriers.
They demonstrated that the immune cells would bind to the melanoma cells even with shear stress conditions similar to those found in the bloodstream. These experiments were all performed in the laboratory and not in the body. The teams intend to perform studies in solid tumors and in animal models next. Dong cautions that this is not a study about curing melanoma, but that it should rather be seen as a first study to show that the technology works. Melanoma cells were used merely to validate the approach, although there are probably other ways to do so.