Enhancing Drug Delivery to Tumors: CendR’s Game
Dr. Erkki Ruoslahti, CNM co-Founder and Distinguished Professor of UCSB and the SBP Medical Discovery Institute, and his colleagues have generated a breakthrough in targeting drugs to cancer.
Their findings, published recently in the journal Science Advances, not only lend insight into how large molecules get into cells, but how a compound the team previously discovered may work to target cancer cells.
More than a decade ago, they found a unique peptide that took only minutes to reach the tumor after being injected into the bloodstream.
Only later, in 2009, having discovered another peptide, iRGD, which had similar properties did they find out what made these peptides special; They included a short string of amino acids in a particular pattern that gave it the ability to penetrate tumors. The pattern, called CendR, has been a major focus of Ruoslhahti’s research.
“The iRGD peptide was special because by using it we could get a drug to go deeper into a tumor and hit all the tumor cells, not just the ones that are close to the blood vessels, which is usually what happens,” said Ruoslahti.
Last year, the group learned even more about iRGD. In Nature Communications, they showed that the peptide triggers a unique mode of transport into the cell, unlike what has been seen before. It does so by binding to a receptor on the cell surface called neuropilin1, which is itself involved in crucial functions, including the movement of fluid and other molecules across walls of blood vessel cells.
There are many ways that molecules can get into cells. iRGD appears to trigger cells to swallow large vesicles. It is similar to a mechanism known as ‘macropinocytosis’ (macro meaning ‘large’; pino ‘drink’; and cyte ‘cell’) yet distinct in some ways, Ruoslahti said.
In the new study, the research team did additional work to characterize CendR’s actions, comparing them with another known peptide technology (TAT) that is often used to get drugs into cells.
The iRGD peptide is undergoing preclinical development, namely mouse toxicology studies that are needed before the team can apply to investigate it in humans. The team has another year’s worth of work ahead. But they already have reason to believe that iRGD might work: it binds to the human version of its receptor. In addition, they have seen promising results after testing the peptide in tumor tissue from people with cancer.
Other authors on the paper are staff scientists Hongbo Pang, Ph.D., and Gary Braun, Ph.D.