CAMBRIDGE, Mass.—The idea of using nanoparticles to deliver oncology drugs directly to tumors, and thus minimize or eliminate chemotherapy side effects, goes back decades. But even with major advances in technology, nanoparticles seem able to delivery only about 1 percent of a drug to its intended tumor target. However, a team of researchers from the Massachusetts Institute of Technology (MIT), the Sanford-Burnham Medical Research Institute and the University of California at San Diego have designed a new type of delivery system that enables communication between nanoparticles in the body and boosted drug delivery to tumors by more than 40 times in a mouse study compared to traditional delivery.
With the new delivery system, an initial wave of nanoparticles is introduced to homes in on the tumor. That wave of nanoparticles then summons a much larger second wave that dispenses the cancer drug. This communication between nanoparticles, the researchers say, is enabled by the body's own biochemistry.
"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 nano-delivery system in the June 19 online edition of Nature Materials. If the new strategy works well in humans, von Maltzahn notes, that would mean enhancing the effectiveness of many drugs not just for cancer but for other diseases.
The senior author of the paper is Sangeeta Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and a member of MIT's David H. Koch Institute for Integrative Cancer Research. She and von Maltzahn drew their inspiration from complex biological systems in which many components work together to achieve a common goal. For example, the immune system works through highly orchestrated cooperation between many different types of cells.
The MIT team's approach is based on the blood coagulation cascade—a series of reactions that starts when the body detects injury to a blood vessel. Proteins in the blood known as clotting factors interact in a complex chain of steps to form strands of fibrin, which help seal the injury site and prevent blood loss.
"There are beautiful examples throughout biology where at a system scale, complex behaviors emerge as a result of interaction, cooperation and communication between simple individual components," says von Maltzahn.
To harness the communication power of that cascade, the researchers needed two types of nanoparticles, notes MIT: signaling ones and receiving ones.
Signaling particles, which make up the first wave, exit the bloodstream and arrive at the tumor site via tiny holes in the leaky blood vessels that typically surround tumors. Once at the tumor, this first wave of particles provokes the body into believing that an injury has occurred at a tumor site, either by emitting heat or by binding to a protein that sets off the coagulation cascade.
Receiving particles are coated with proteins that bind to fibrin, which attracts them to the site of blood clotting. Those second-wave particles also carry a drug payload, which they release once they reach the tumor.
In a study of mice, one system of communicating nanoparticle systems delivered 40 times more doxorubicin (a drug used to treat many types of cancer) than non-communicating nanoparticles. The researchers also saw a correspondingly amplified therapeutic effect on the tumors of mice treated with communicating nanoparticles.
To pave the path for potential clinical trials and regulatory approval, the MIT researchers are now exploring ways to replace components of these cooperative nanosystems with drugs already being tested in patients. For example, drugs that induce coagulation at tumor sites could replace the signaling particles tested in this study.
Original source: Anne Trafton, MIT News Office
With the new delivery system, an initial wave of nanoparticles is introduced to homes in on the tumor. That wave of nanoparticles then summons a much larger second wave that dispenses the cancer drug. This communication between nanoparticles, the researchers say, is enabled by the body's own biochemistry.
"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 nano-delivery system in the June 19 online edition of Nature Materials. If the new strategy works well in humans, von Maltzahn notes, that would mean enhancing the effectiveness of many drugs not just for cancer but for other diseases.
The senior author of the paper is Sangeeta Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and a member of MIT's David H. Koch Institute for Integrative Cancer Research. She and von Maltzahn drew their inspiration from complex biological systems in which many components work together to achieve a common goal. For example, the immune system works through highly orchestrated cooperation between many different types of cells.
The MIT team's approach is based on the blood coagulation cascade—a series of reactions that starts when the body detects injury to a blood vessel. Proteins in the blood known as clotting factors interact in a complex chain of steps to form strands of fibrin, which help seal the injury site and prevent blood loss.
"There are beautiful examples throughout biology where at a system scale, complex behaviors emerge as a result of interaction, cooperation and communication between simple individual components," says von Maltzahn.
To harness the communication power of that cascade, the researchers needed two types of nanoparticles, notes MIT: signaling ones and receiving ones.
Signaling particles, which make up the first wave, exit the bloodstream and arrive at the tumor site via tiny holes in the leaky blood vessels that typically surround tumors. Once at the tumor, this first wave of particles provokes the body into believing that an injury has occurred at a tumor site, either by emitting heat or by binding to a protein that sets off the coagulation cascade.
Receiving particles are coated with proteins that bind to fibrin, which attracts them to the site of blood clotting. Those second-wave particles also carry a drug payload, which they release once they reach the tumor.
In a study of mice, one system of communicating nanoparticle systems delivered 40 times more doxorubicin (a drug used to treat many types of cancer) than non-communicating nanoparticles. The researchers also saw a correspondingly amplified therapeutic effect on the tumors of mice treated with communicating nanoparticles.
To pave the path for potential clinical trials and regulatory approval, the MIT researchers are now exploring ways to replace components of these cooperative nanosystems with drugs already being tested in patients. For example, drugs that induce coagulation at tumor sites could replace the signaling particles tested in this study.
Original source: Anne Trafton, MIT News Office
