Masked Nanoparticles Come out to fight cancer
Specialists of the newly created BIND Biosciences company, based in Cambridge, Massachusetts, have developed a new technological process that allows to obtain nanoparticles filled with antitumor drugs and coated with proteins that ensure their targeted delivery to the tumor area. They hope that the use of new nanoparticles will reduce the severity of adverse side effects of chemotherapy drugs and at the same time increase their effectiveness.
BIND Biosciences specialists have demonstrated that the use of a new nanoparticle-based targeted drug delivery system makes it possible to fight prostate, breast and lung tumors in rodents more effectively than traditional methods of treatment. The nanoparticles created by them remain in the bloodstream for more than a day, which increases the likelihood of their getting into the tumor zone. Currently, the company is preparing for the start of clinical trials scheduled for next year, and is working on improving the technological process of mass production of carrier nanoparticles.
The figure shows nanoparticles filled with chemotherapy (colored pink) accumulated in prostate cancer cells (cells are colored green, their nuclei are blue). The particles are designed to target prostate cancer cells.
The approach chosen by the company's specialists is based on the use of self-assembling polymers developed by the laboratory of Robert Langer, professor of chemical technology at the Massachusetts Institute of Technology. In 2006, Langer co-founded BIND Biosciences with Omid Farokhzad, a researcher and practicing physician at Harvard University Medical School.
The effect of several existing and currently under development drugs is based on the use of lipid nanoparticles, or other approaches that prolong the time the drug is in the bloodstream. This ensures that more drugs get into the target tissues. However, none of the existing approaches makes it possible to deliver the drug to the target cells, while simultaneously increasing its circulation period.
The core of the nanoparticles developed by BIND Biosciences consists of biodegradable polymers: polylactic acid (PLA) and copolylactic/glycolic acid (copolylactic acid/glycolic acid, PLGA), which hold the molecules of the chemotherapy drug inside a molecular "network" that ensures its slow release. The outer layer of nanoparticles is made of polyethylene glycol, the properties of the molecules of which allow them to avoid interactions with various proteins and immune cells during circulation in the bloodstream. This masking coating is coated with molecules of specially designed guiding proteins that selectively bind to target cells and ensure the delivery of the "cargo" of nanoparticles to their intended destination.
When all three components are mixed under precisely regulated chemical conditions, spontaneous self-assembly of nanoparticles occurs. According to Farokhzad, such an easy process, which does not require numerous stages of complex chemical synthesis, makes it possible to produce literally kilograms of nanoparticles, which no one has ever been able to do before. The manufacturing technology of most other targeted nanoparticles begins with the synthesis of the nucleus, which is subsequently covered with "guiding" molecules. This process is quite complex and difficult to reproduce.
Imitating drug manufacturers who select compounds with optimal properties during screening of thousands of candidate molecules, BIND Biosciences employees synthesize hundreds of variants of nanoparticles for each drug, after which they conduct screening, the purpose of which is to identify nanoparticles that linger in the bloodstream for as long as possible and most successfully reach the target tissue. Small changes in the concentrations of each of the three components make it possible to change the size, surface charge of nanoparticles and the concentration of guiding molecules on their surface.
This approach allows you to choose the optimal ratio of the characteristics of nanoparticles. Traditionally, researchers try to load nanoparticles with as many guiding protein ligands as possible, but Langer and Farokhzad found that in fact a small number of these molecules perform their task better, since their excess accelerates the removal of nanoparticles from the bloodstream.
To date, researchers have already tested their technology on 15 anticancer agents and drugs for the treatment of cardiovascular and inflammatory diseases, but they pay special attention to working with chemotherapy drugs. Testing of nanoparticles loaded with chemopreparations on mice that were vaccinated with human tumors showed that 12 hours after administration of the drug, its concentration in the tumors of the experimental group of animals was 20 times higher than in the tumors of the control group of mice that were injected with a pure chemopreparation. The introduction of the nanotechnological version of the drug suppressed the growth of tumors of the breast, prostate and lung much more effectively than the introduction of the drug itself, or nanoparticles loaded with it that do not have guiding protein molecules on their surface.
Of the results presented by the authors at a conference held in October by the US National Cancer Institute, experts were most impressed by the increase in the circulation time of the drug in the bloodstream from the usual 3-6 hours to 24-72 hours provided by the new nanoparticles.
The company has not yet announced either the drug or the type of cancer whose treatment will be the task of clinical trials planned for next year. It is only known that she is working to increase the productivity of the technological process, and is also negotiating with pharmaceutical companies (whose names are also kept secret) in order to select drugs, including those postponed until better times due to dangerous side effects or other problems that can be solved using the above technology.
Evgenia Ryabtseva, Alexander Chubenko
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of Technology Review: Stealthy Nanoparticles Attack Cancer Cells.
10.11.2009