Unleashing the Power of Peptides

One of biggest challenges in cancer diagnostics and therapeutics is being able to differentiate tumor cells from normal cells, and this is an issue that USC School of Pharmacy Research Assistant Professor Jennica Zaro will be tackling with support from a new grant from the National Institutes of Health.

The NIH’s National Cancer Institute has awarded Zaro a two-year grant totaling $348,272 for her project titled “Mildly Acidic Tumor Microenvironment for Diagnostic and Therapeutic Nanomedicine.”

Zaro’s research expands on current knowledge that areas near tumors are mildly acidic, a fact that has been known for a long time but not yet fully exploited.

“Targeting a mildly acidic range is not a new area of study, but we’re doing it differently,” she explains. “In our approach we’re using small peptide sequences which become activated in even mildly acidic (low pH) environments.”

Her work uses small peptide sequences that are very sensitive to the pH range that exists near solid tumor cells. Using nanotechnology, Zaro has created a specific masking sequence of amino acids that will prevent the peptides from entering healthy cells, while allowing them to enter or bind to tumor cells. When just circulating along normal cells, these peptide sequences do not enter or bind to the cell, but when they enter lower pH areas, they activate the peptide carrier, resulting in surface binding to tumor cells and higher cell internalization.

“The project will pursue two parallel tracks,” explains Zaro. “The first is to use these peptide sequences as diagnostic imaging agents to locate the cancer cells. Then, we can optimize the carrier to deliver a therapeutic agent to these cells for treatment.”

This method is more precise than many currently used methods that are not able to recognize the small differences in pH levels near tumor cells. As a result, tumor cells in mildly acidic areas are often missed. Since it is more sensitive in mildly acidic environments, Zaro’s structure overcomes this shortfall. Another advantage is that the body is used to degrading these particular peptides, so utilizing them to target and treat cancer shouldn’t have long term side effects.

The NIH grant is building on a previous grant Zaro received from the USC Ming Hsieh Institute for Research of Engineering-Medicine for Cancer. The funding will be used to see if her methods can be effective when applied in vivo.

“Overall, we are trying to understand cancer cells and why they keep growing, and to use that information to prevent and treat cancer,” says Zaro.

The project will focus on breast cancer but is applicable to most other cancers. The grant is an NIH R21.