Treating tumors with nanoparticles has been challenging because immune cells called mononuclear phagocytes identify them and yank them from circulation, preventing the nanomaterials from reaching their target. Recently, a team of researchers in California and Massachusetts has developed a “cocktail” of different nanometer-sized particles that work in concert within the bloodstream to locate, adhere to and kill cancerous tumors.
In the study, the researchers developed a system containing two different nanomaterials the size of only a few nanometers, or a thousand times smaller than the diameter of a human hair, that can be injected into the bloodstream. One nanomaterial was designed to find and adhere to tumors in mice, while the second nanomaterial was fabricated to kill those tumors.The team had previously designed nanometer-sized devices to attach to diseased cells or deliver drugs specifically to the diseased cells while ignoring healthy cells. But the functions of those devices, the researchers discovered, often conflicted with one another. That is, a nanoparticle that is engineered to circulate through a cancer patient’s body for a long period of time is more likely to encounter a tumor. However, that nanoparticle may not be able to stick to tumor cells once it finds them. Likewise, a particle that is engineered to adhere tightly to tumors may not be able to circulate in the body long enough to encounter one in the first place.
Hence two graduate students, Ji-Ho Park from UC San Diego laboratory and Geoffrey von Maltzahn from Bhatia’s MIT laboratory has headed the endeavor towards developing two distinct nanomaterials that would work in concert to overcome these obstacles.
The first particle is a gold nanorod “activator’ that accumulates in tumors by seeping through its leaky blood vessels. The gold particles cover the whole tumor and behave like an antenna by absorbing otherwise benign infrared laser irradiation, which then heats up the tumor. After the nanorods had circulated in the bloodstream of mice that had epithelial tumors for three days, the researchers used a weak laser beam to heat the rods that attached to the tumors. This sensitized the tumors, and the researchers then sent in a second nanoparticle type, composed of either iron oxide nanoworms or doxorubicin-loaded liposomes. This “responder” nanoparticle was coated with a special targeting molecule specific for the heat-treated tumor.
“While one type of nanoparticle improves detection of the tumor, he said, the other is designed to kill the tumor. The researchers designed one type of responder particle with strings of iron oxide, which they called “nanoworms,” that show up brightly in a medical magnetic resonance imaging, or MRI, system. The second type is a hollow nanoparticle loaded with the anti-cancer drug doxorubicin”. With the drug-loaded responder, the scientists demonstrated in their experiments that a tumor growing in a mouse can be arrested and then shrunk. “The nanoworms would be useful to help the medical team identify the size and shape of a tumor in a patient before surgery, while the hollow nanoparticles might be used to kill the tumor without the need for surgery,” said Michael Sailor, a professor of chemistry and biochemistry at the University of California, San Diego and the primary author of a paper.
The project was funded by grants from the National Cancer Institute of the National Institutes of Health