A UCSB researcher recently received a $3.8 million grant from the Dept. of Defense to continue his work developing probes that can target cancer cells.

Erkki Ruoslahti — a professor of molecular, cellular and developmental biology who is affiliated with UCSB’s Burnham Institute for Medical Research — was granted the Innovator Award for his discovery of ways to target drugs to tumor blood vessels and then suppress the growth of those tumors. The grant will be distributed to Ruoslahti over five years.

According to a press release, in Ruoslahti’s experiments with mice he figured out a way to engineer nanoparticles that form a targeted payload delivery system to tumors in the body. This development in nanomedicine, the release said, could potentially be used to increase the effectiveness of cancer therapies while decreasing side effects.

Ruoslahti said the targeting system he designed uses a peptide – a section of proteins which binds only to certain tissues - to focus on tumor blood vessels as well as the interior of the tumor.

“[We are] using compounds that bind to tumor blood vessels,” Ruoslahti said. “We can put a payload on the compound, which accumulates at the target.”

The peptide, he said, has the potential to carry a variety of targeted chemicals into the body.

“The nanoparticles can carry an imaging contrast agent, such as those used for MRI,” Ruoslahti said. “They can also carry a drug.”

According to Ruoslahti, his research can be used to improve drug delivery and decrease the incidence of side effects.

“We can get more of the drug or more [of the] imaging agent into the tumor, which means that less will go elsewhere,” Ruoslahti said. “The end result is higher efficacy and fewer side effects.”

The particles can be used to essentially strangle and kill a tumor by preventing blood flow to the cancer cells, Ruoslahti said.

“We have a peptide that binds to clotted plasma proteins, which are present in tumors,” Ruoslahti said. “The vascular wall and the interior of tumors have clotted plasma. If we send particles coated with clot-binding peptides into a tumor, these particles cause more clotting, allowing more particles to bind, causing more clotting and so on. When tumor [blood] vessels experience enough clotting, it will cut off blood circulation to the tumor, meaning that the tumor would not survive.”

The targeted particles can bypass the tumor’s defenses, allowing the anti-cancer payload to penetrate the tumor and better attack the cancer cells.

“In tumors, high interstitial pressure causes fluid to flow out of the tumor,” Ruoslahti said. “Getting a drug to go into a tumor is like swimming upstream. However, we have found targeting probes that penetrate into tumors and can also take a payload there. In some cases we package a drug in nanoparticles and send the package into the tumor.”

In the future, Ruoslahti said, he plans to develop a method to activate the particles on command by linking the particles to a trigger.

“We are working on a system where nanoparticles could release their drug payload on demand,” Ruoslahti said.

The current method of activation involves using heat. Ruoslahti’s lab is also looking into magnetic triggers which penetrate the body more evenly.