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Optimization of pH-sensitive peptide nanoconstructs for use in targeting the mildly acidic tumor microenvironment

Year:

Investigators: Jennica Zaro, Ph.D. Peter Conti, M.D., Ph.D.
Innovation: a method to recognize the minute differences in pH levels near tumor cells
Clinical significance: enabling more powerful cancer-killing drugs to be used without side effects

Investigators: Jennica Zaro, Ph.D. Peter Conti, M.D., Ph.D.
Innovation: a method to recognize the minute differences in pH levels near tumor cells
Clinical significance: enabling more powerful cancer-killing drugs to be used without side effects

One of biggest challenges in cancer care is differentiating tumor cells from normal ones. This research builds upon the knowledge that areas near tumors are mildly acidic, a fact that has been long known but not yet fully exploited. The approach uses small peptide sequences that become activated in even mildly acidic — low pH — environments.

Using nanotechnology, the USC team has created a specific masking sequence of amino acids that prevents peptides from entering healthy cells, while allowing them to enter or bind to tumor cells. When circulating along normal cells, these peptide sequences travel along without incident. However, lower pH areas activate the peptide carrier, which binds to the tumor cell surface or is internalized by the tumor cells.

The research pursues therapeutic as well as diagnostic objectives. After using the peptide sequences as imaging agents to locate cancer cells, the team aims to optimize the carrier to deliver treatments to the malignancies. The approach solves a problem inherent in current methods that fail to recognize the minute differences in pH levels near cancer cells, causing many tumors to be overlooked.