The key to this research was the discovery that combining two different nanoparticles – one to find and adhere to the cancerous cells and the other to kill the cells – actually worked. Typically nanoparticles in the bloodstream have a hard time staying active, either because they break down, or because the body’s own defense mechanisms, immune cells called mononuclear phagocytes, remove them. By working two nanoparticles in tandem, the researchers were able to improve the amount of time the ‘cocktail’ stays active in the bloodstream, meaning the longer time the particles have to reach the target cancer.

“This study represents the first example of the benefits of employing a cooperative nanosystem to fight cancer,” said Michael Sailor, a professor of chemistry and biochemistry at the University of California, San Diego and the primary author of a paper describing the results, which is being published in a forthcoming issue of the Proceedings of the National Academy of Sciences.

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 Sailor.

[Source: University of California San Diego]

This research is the first time a combination of nanoparticles has been used (successfully) in test animals. Like much of nanomedicine, the application of this approach in human cases is a way off (possibly years).

The key to this research was the discovery of a peptide (a chain of amino acids) called iRGD that has some very important properties: It binds directly to the blood vessels of cancerous tissue, and more importantly, can actually penetrate the outer membrane of cancer cells. This makes iRGD an ideal delivery medium for nanoparticles of anti-cancer drugs.

Led by Erkki Ruoslahti, M.D., Ph.D., distinguished Burnham professor at UCSB, this research was built on Dr. Ruoslahti’s previous discovery of “vascular zip codes,” which showed that blood vessels in different tissues (including diseased tissues) have different signatures. These signatures can be detected and used to dock drugs onto vessels inside the diseased tissue. In addition to homing in on tumor vessels, the new iRGD peptide penetrates them to bind inside the tumor. Previous peptides have been shown to recognize and bind to tumors, but were unable to go beyond the tumor blood vessels.

“This peptide has extraordinary tumor-penetrating properties, and I hope that it will make possible substantial improvements in cancer treatment,” says Dr. Ruoslahti. “In our animal studies, the iRGD peptide has increased the efficacy of a number of anti-cancer drugs without increasing their side effects. If these animal experiments translate into human cancers, we would be able to treat cancer more effectively than before, while greatly reducing the side effects the patient would suffer.”

Iron oxide nanoworms, which can be visualized by magnetic resonance imaging, were coupled to the peptide and shown to penetrate the tumors, whereas uncoupled nanoworms could not. This demonstrates that iRGD can deliver diagnostics to tumors. The anti-cancer drug Abraxane was also shown to target, penetrate and spread more within tumor tissue when coupled to iRGD than with other formulations.

[Source: Burnam Institute]

Some experimenting with iRGD and animals has taken place, but it should be emphasized that this is a very early phase of testing. Many other cancer drugs and other combinations of iRGD will be on the docket for research. The road to testing and use with humans is still a long journey.