Tumor-Associated Enzyme Triggers Drug Release From Nanoparticles
Cancer cells display a variety of proteins on their outer membranes that are not present on the surface of normal cells. Although these proteins are likely to be critical to the survival or metastatic spread of cancer, investigators at North Dakota State University have turned one of these proteins against the malignant cell, using it to trigger the release of dye molecules entrapped in a nanoparticle. The results make possible the development of nanoparticles that will release antitumor drugs only when encountering malignant cells, not healthy cells.
Reporting its work in the journal Bioconjugate Chemistry, a research team headed by D.K. Srivastava, Ph.D., and Sanku Mallik, Ph.D., created liposomes containing peptides resembling collagen, the major structural protein that holds cells together. These peptides are substrates for matrix metalloproteinase-9 (MMP-9), an enzyme linked to the ability of many types of cancer cells to break off from a primary tumor and spread throughout the body. When the peptide-studded liposome encounters MMP-9, the enzyme begins digesting the peptide, causing the liposome to fall apart. In the current experiments, the investigators loaded the liposomes with a fluorescent dye that when released produces a characteristic optical signal. These liposomes remain intact when exposed to other protein-degrading enzymes.
The investigators also found that this triggered release is self-limiting. Once the liposome falls apart, the remaining peptides bind to and inactivate MMP-9. This self-limiting property would serve to limit the amount of drug released at each tumor cell.
This work, which was supported in part by the National Cancer Institute, is detailed in the paper, “Matrix metalloproteinase-assisted triggered release of liposomal contents.” An abstract of this paper is available through PubMed.View abstract