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 tumour vessels, the new iRGD peptide penetrates them to bind inside the tumour. Previous peptides have been shown to recognise and bind to tumours, but were unable to go beyond the tumour blood vessels.
"This peptide has extraordinary tumour-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."
The novel iRGD peptide, identified by using phage display for a peptide that binds to the blood vessels of pancreatic and bone tumours, was tested to determine its ability to penetrate tumours. Researchers injected fluorescent-labelled iRGD into tumour-bearing mice and found that the peptide accumulated in a variety of tumours, including prostate, breast, pancreatic, brain and other types. In addition, the peptide only targeted the tumours and did not accumulate in normal tissue.
Iron oxide nanoworms, which can be visualised by magnetic resonance imaging, were coupled to the peptide and shown to penetrate the tumours, whereas uncoupled nanoworms could not. This demonstrates that iRGD can deliver diagnostics to tumours. The anti-cancer drug Abraxane was also shown to target, penetrate and spread more within tumour tissue when coupled to iRGD than with other formulations.
