To minimize the toxic effects of chemotherapy, many researchers have been working to develop nanoparticles that that deliver drugs directly to tumors. But researchers at MIT claim that even the best of these nanoparticles are typically only able to deliver about one percent of the drug to their intended target. Now, a team has developed a new delivery system that sees a first wave of nanoparticles homing in on a tumor that then calls in a larger second wave that dispenses the cancer drug. In a mouse study, the new approach was found to boost drug delivery to tumors by over 40-fold.
Taking inspiration from complex biological systems, such as the immune system, that see many components working together to achieve a common goal, the team based their new approach on the blood coagulation cascade. This is a series of reactions that starts when the body detects injury to a blood vessel and clotting factor proteins in the blood interact in a complex chain of steps to form strands of fibrin, which help seal the injury site and prevent blood loss.
To develop a similar approach that takes advantage of the body's own biochemistry to target tumors the researchers developed two types of nanoparticles - signaling and receiving.
The signaling nanoparticles, which make up the first wave, work in the same way that most targeted nanoparticles reach their target. They exit the bloodstream and arrive at the tumor site via tiny holes in the leaky blood vessels that typically surround tumors. Once there, they provoke the body into believing that an injury has occurred at the tumor site, either by emitting heat or by binding to a protein that sets off the coagulation cascade.
The receiving nanoparticles are coated with proteins that bind to fibrin, which attracts them to the site of the blood clotting. These second-wave nanoparticles also carry a drug payload, which is released once they reach the tumor.
In a mouse study, one of the communicating nanoparticle systems delivered 40 times more doxorubicin - a drug used to treat many different types of cancer - than non-communicating nanoparticles. There was also a correspondingly amplified therapeutic effect on the tumors of mice treated with the communicating nanoparticles.
In an effort to pave the way for potential clinical trials and regulatory approval, the researchers are also examining ways to replace components of the new approach with drugs that are already being tested in patients. They say drugs that induce coagulation at tumor sites could be used in place of the signaling nanoparticles tested in the study, for example.
The research team, made up of researchers from MIT, the Sanford-Burnham Medical Research Institute, and the University of California at San Diego, say this new approach could be used to enhance the effectiveness of many drugs used to combat cancer as well as other diseases.
"What we've demonstrated is that nanoparticles can be engineered to do things like communicate with each other in the body, and that these capabilities can improve the efficiency with which they find and treat diseases like cancer," says Geoffrey von Maltzahn, a former MIT doctoral student now at Cambridge-based Flagship VentureLabs, and lead author of a paper describing the system in the June 19 online edition of Nature Materials.
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