July 8, 2011 | 4
Research published in Nature Materials this month takes lessons from cooperation in nature, including that observed in insect swarms, to create better targeting methods for cancer therapeutics . "Smart" anticancer drug systems can use mechanisms similar to swarm intelligence to locate sites of disease in the human body. Swarm intelligence arises when swarm behavior, for example bees flying and working together to locate sources of food, is used by the group "to solve a problem collectively, in a way that the individuals cannot" .
Insect swarms indeed often come up with solutions to a common task or problem that are "better than those produced through the most advanced mathematics" . When researchers like Geoffrey von Maltzahn at MIT take lessons from swarm behavior and other examples of cooperation in nature (Figure 1), the results are engineered systems that have the potential to revolutionize the diagnosis and treatment of various cancers. Group or "swarm" problem-solving can handle the task of locating small collections of cancer cells inside a human body containing more than 100 trillion non-cancerous cells!
Geoffrey von Maltzahn and coworkers have designed a two-part system consisting of specialized nanoparticles that communicate with each other to amplify the delivery of drugs to sites of disease (Figure 2). Nanoparticles are very small objects, less that 1/1,000 the width of an average human hair, that can interact with individual human cells, proteins and even single molecules. Nanoparticles can also be modified in their shape, size and surface properties to remain in the bloodstream long enough to accumulate mostly in tumor tissues, which have leakier blood vessels than normal tissues.
Nanoparticles are thus excellent candidates for the transport of drugs to sites of disease. However, individual nanoparticles, even when equipped with "homing" molecules that lead them preferentially to cancer cells and tumorous tissues, still leave much to be desired in their targeting efficiency. Targeting efficiency is a measure of how well nanoparticles accumulate in cancer tissues.
Typically, drug-loaded nanoparticles must be delivered in the trillions to a subject animal  in order to reach even minimum therapeutic levels in a small, deep-seated tumor. This is a huge waste of nanoparticle agents and drug compounds, which not only are expensive and often hard to make, but also may do harm to healthy parts of the body when injected in such high numbers.
While many methods have been devised to improve the targeting efficiency of nanoparticles for disease diagnosis and therapy, Geoffrey von Maltzahn and coworkers may have come up with the most ingenious solution yet. They have created "scouting" or Signaling nanoparticles that pave the way to the location of a tumor inside a living mouse, and then communicate the tumor location to Receiving nanoparticles, or the rest of the "swarm." This mechanism is similar to bee logic, where a bee swarm is able to "fly directly to a target that has been identified by (bee) scouts" .
Once the Signaling nanoparticles have recognized the presence of a tumor, they send signals to the drug-loaded Receiving nanoparticles broadcasting the tumor site . In this way, just one scout is able to recruit more than 150 drug-loaded Receiver nanoparticles, equivalent to more than 35,000 individual drug molecules. This is an incredible amplification, similar to how a single "leader" or scout bee can recruit a whole beehive’s worth of his companions to a feeding site.
Figure 2. Left: Figure compiled by Paige Brown, ClipArt & Wiki commons. Right: Credit Ji Ho (Joe) Park, PhD. A cooperative nanosystem consisting of liposomes (white circle) and gold nanorods (black).
In another analogy, the author of The Perfect Swarm, Len Fisher, points out that leadership of small military groups can engage a whole army in a "swarm behavior" effect. It is exactly this type of swarm behavior, where signaling between components takes the form of a cascading chain of communications, that helps two-component Signaling-Receiving nanoparticle systems to amplify drug delivery to cancerous lesions. The nanoparticles designed by Geoffrey von Maltzahn and coworkers communicate with each other through the coagulation cascade, a complex biological cascade of reactions that causes blood to form clots and prevent excessive bleeding.
Signaling nanoparticles consisting of gold nanorods initiate the blood coagulation process through light-activated heating at the tumor site. When medical researchers shine a near-infrared laser onto a tumor site in a living mouse, gold nanorods quickly heat up and initiate blood clotting through heat damage to tumor blood vessels. Drug-loaded liposome nanoparticles (the Receivers) then react to this coagulation cascade by promoting a step near the end of the cascade that produces fibrin, the stringy protein that forms the mesh of a blood clot over a wound.
Through such communication, Receiving liposome nanoparticles, as the cancer-fighting troops, are attracted to the tumor site by small numbers of Signaling or scout gold nanorod particles (Figure 2). Coagulation is a highly conserved process in biology, and thus nanoparticles that communicate through this pathway can aid in the enhancement of cancer-targeting therapies across wide animal and human populations.
The results of Geoffrey von Maltzahn et al. in their Nature Materials publication reveal that nanoparticles that communicate with each other can deliver more than 40-fold higher doses of chemotherapeutics (anti-cancer drugs) to tumors than nanoparticles that do not communicate can deliver. These results show the potential for nanoparticle communication to amplify drug delivery over that achievable by nanoparticles that work alone, similar to how insect swarms perform better as a group than the individual insects do on their own.
While further experiments and pre-clinical studies will be required to validate that nanoparticle communication through complex pathways such as coagulation are safe for humans and do not produce unforeseen side effects, the application of swarm intelligence to cancer targeting holds enormous potential for improved therapies.
 Geoffrey von Maltzahn et al. Nanoparticles that communicate in vivo to amplify tumour targeting. Nature Materials 10, 545–552 (2011) doi:10.1038/nmat3049
 The Perfect Swarm: The Science of Complexity in Everyday Life, Len Fisher, Ph.D. Basic Books 2009
 Yucai Wang, Paige Brown & Younan Xia. Nanomedicine: Swarming towards the target. Nature Materials 10, 482–483 (2011) doi:10.1038/nmat3060
About the Author: Paige Brown is a recent Ph.D. student in biomedical engineering at Washington University in St. Louis. She also holds a B.S. and M.S. degrees in Biological and Agricultural Engineering from Louisiana State University, where she plans to return in 2012 to pursue an advanced degree in journalism. Paige is the author of the popular science blog From The Lab Bench, hosted on Nature Network. Although a scientist by trade, she is a writer at heart. You can follow her on Twitter.
The views expressed are those of the author and are not necessarily those of Scientific American.
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