Nanoparticles (shown in pink) developed by BIND Biosciences accumulate in a prostate-cancer cell. (Photo by BIND Biosciences.)
Scientists at BIND Biosciences (Cambridge, MA) have shown that biodegradable polymer–based nanoparticles infused with drugs and encased in cancer-targeting proteins can impede the growth of prostate, breast, and lung tumors in rodents. Capable of remaining in the bloodstream for more than a day, the nanoparticle technology increases the likelihood that cancer-fighting drugs will reach their targets. The company hopes that the system will diminish the side effects of chemotherapy while killing tumors.
Some drugs on the market and in development use lipid-based nanoparticles and other technologies to extend the lifespan of cancer-fighting drugs in the bloodstream, allowing more medication to reach the target tissue through the blood vessels. But none of these formulations can target specific cells, and none enjoy extended circulation time. In addition, in most targeted nanotechnologies, the core particle is made first and later coated with the targeting molecule, a complex process offering limited repeatability.
As reported in Technology Review, published by the Massachusetts Institute of Technology (MIT; Cambridge, MA), BIND’s approach is based on the self-assembling biodegradable polymers polylactic acid and copolylactic acid/glycolic acid, which hold the desired drug in a molecular mesh, enabling it to diffuse slowly. Developed in the lab of Robert Langer, a professor of chemical engineering at MIT, the nanoparticles contain an outer layer that is made of polyethylene glycol, a molecule with water-like properties that lets the nanoparticle evade detection by proteins and the white blood cells that destroy pathogens in the blood. That stealth coating is also dotted with specially designed peptides, which bind to cells of interest.
When the three components are mixed together, structured nanoparticles form spontaneously. “Because the self assembly doesn’t require multiple complicated chemical steps, the particles are very easy to manufacture,” explains Omid Farokhzad, a scientist and physician at Harvard Medical School (Boston) and cofounder of BIND with Langer in 2006. “And we can make them on a kilogram scale, which no one else has done.”
Mimicking the screening process that drug developers use to find the optimal candidate molecule, researchers at BIND have generated hundreds of versions of nanoparticles for each drug and then screened them to find those that can survive in the bloodstream the longest and have the best tissue-targeting capabilities. By varying the concentrations of the three nanoparticle components, the researchers can generate particles with different sizes, surface charges, and concentrations of targeting molecules on their surface.
While focusing on chemotherapeutics, BIND Scientists have tested the technology using 15 different drugs for cancer, cardiovascular disease, and inflammatory diseases. Testing the particles in mice that have been engineered to have human tumor cells, researchers showed that the animals treated with the nanoparticles had as much as 20 times more drug in the tumor 12 hours after delivery than did animals given the drug alone. The nanotech version of the drug was also able to stop the growth of breast, prostate, and lung tumors more effectively than either the drug alone or the drug delivered via nanoparticles lacking the targeting molecules.
According to results presented last month at a conference at the National Cancer Institute (Bethesda, MD), BIND scientists have now increased circulation time from three to six hours to 24 to 72 hours. In preparation for clinical trials in cancer patients next year, the company is refining a method for making large volumes of its nanoparticle-based delivery system.
For a video detailing BIND’s method for manufacturing the nanoparticles, click here.
Tags: cancer treatment, nanoparticles
