A little-known enzyme might hold the key to cancer drug targeting

A type of enzyme that you’ve probably never heard of, called matrix metalloproteinase (MMP), could be key to the development of ‘smart’ cancer drugs. In a review article published recently in the journal Trends in Pharmacological Sciences, Lin Zhu, PhD, an assistant professor at the Texas A&M Irma Lerma Rangel College of Pharmacy, and his colleagues explained the potential of these enzymes.

“Because of high correlation between the MMP expression and cancer malignancy, the well-identified MMPs have been used as important cancer biomarkers,” Zhu said. In other words, because they are overexpressed in cancer, their presence is a good indication of the occurrence of cancer. MMPs have been investigated as therapeutic targets, but MMP inhibitor drugs tend to be so toxic that they do more harm than good.

Lately, a renewed interest in MMPs as stimuli for ‘smart’ tumor-targeted drug delivery has emerged. These therapies could be engineered to be responsive to MMPs, but—unlike the toxic drugs of the past—do not inhibit the enzyme. Instead, they would use MMPs to recognize which cells are cancerous so they can deliver targeted drugs only to cancerous tissues and cells. A similar strategy could also deliver imaging agents to better view the number and location of cancerous tumors.

Zhu’s lab focuses on developing novel drug delivery systems and nanomedicines, particularly these MMP-responsive nanocarriers. “We are exploring various strategies for targeting tumor tissue, tumor cells and the intracellular compartments of the tumor cells,” Zhu said. “We are characterizing and evaluating these nanocarriers, including the stability, MMP responsiveness, drug loading and release, tumor targeting and other properties. We are also studying various platforms for delivery.”

In addition to approaches using MMP-responsive materials for cancer diagnosis and treatment, Zhu and his team are preparing and testing the MMP-responsive nanomaterials for new functions, such as for the treatment of other diseases.

“Currently, we are entering the era of smart, stimuli-responsive drug delivery that can respond to subtle alterations in the tumor’s microenvironment,” Zhu said. MMP-responsive nanoparticles show promising features in terms of targeted drug delivery and on-demand drug release in preclinical studies, but so far, there has been little work toward clinical translation.

“The MMP-responsive strategy is great but still in its early stage,” Zhu said. “More studies are needed before it can really benefit the patients suffering from cancer. My hope is that more researchers will work on MMPs and help this promising approach move forward, as a growing body of evidence indicates that the MMP-responsive strategy has great potential for effective and smart drug delivery and tumor targeting.”