Tumor-Homing Peptide Enhances Delivery of Anticancer Drugs

Insertion of an anticancer medicine directly into a tumor may be possible, if the drug is attached to the tumor-homing peptide iRGD.

Investigators at the Burnham Institute for Medical Research (Santa Barbara, CA; USA) have extended earlier studies on the unique molecular signatures of tumor vascular systems by creating a peptide that would specifically bind to these sites. Furthermore, the novel structure of iRGD enables molecules that are conjugated to it to be transported from the tumor vascular system into the tumor itself.

Initially, the investigators injected fluorescent-labeled iRGD into tumor-bearing mice. They found that the peptide accumulated in a variety of tumors, including prostate, breast, pancreatic, and brain. Importantly, the peptide only targeted the tumors and did not accumulate in normal tissue. In another study, the investigators attached iron oxide "nanoworms" to iRGD and injected the molecular complexes into tumor-bearing mice. Magnetic resonance spectrometry then showed that the tumors in the mice that received the complexes absorbed the nanoworms, while mice receiving nanoworms not bound to iRGD failed to absorb them. Finally, they showed that conjugation to iRGD significantly enhanced the activity of an antitumor drug.

In their paper published in the December 8, 2009, issue of the journal Cancer Cell, the investigators suggested that iRGD homes to tumors through a three-step process: the RGD motif mediates binding to integrins on the tumor endothelium and a proteolytic cleavage then exposes a binding motif for neuropilin-1, which mediates penetration into tissue and cells.

"This peptide has extraordinary tumor-penetrating properties, and I hope that it will make possible substantial improvements in cancer treatment,” said senior author Dr. Erkki Ruoslahti, professor of biological sciences at the Burnham Institute for Medical Research. "In our animal studies, the iRGD peptide has increased the efficacy of a number of anticancer 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.”

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Burnham Institute for Medical Research