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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.
About National Cancer Institute
To help meet the goal of reducing the burden of cancer, the National Cancer Institute (NCI), part of the National Institutes of Health, is engaged in efforts to harness the power of nanotechnology to radically change the way we diagnose, treat and prevent cancer.
The NCI Alliance for Nanotechnology in Cancer is a comprehensive, systematized initiative encompassing the public and private sectors, designed to accelerate the application of the best capabilities of nanotechnology to cancer.
Currently, scientists are limited in their ability to turn promising molecular discoveries into benefits for cancer patients. Nanotechnology can provide the technical power and tools that will enable those developing new diagnostics, therapeutics, and preventives to keep pace with today’s explosion in knowledge.
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