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Nanoparticle Self-Assembly Triggered by Tumor-Associated Enzyme

Date: 1.6.2007 

There is a growing recognition among cancer researchers that the most accurate methods for detecting early-stage cancer will require the development of sensitive assays that can identify simultaneously multiple biomarkers associated with malignant cells. Now, using sets of nanoparticles designed to aggregate in response to finding more cancer biomarkers, a team of researchers funded by the Alliance for Nanotechnology in Cancer has developed a multiplexed analytical system that could detect cancer using standard magnetic resonance imaging (MRI). Sangeeta Bhatia, M.D., Ph.D., a joint member of the Centers for Cancer Nanotechnology (CCNE) based at both the University of California, San Diego (UCSD) and MIT-Harvard, and Michael Sailor, Ph.D., a member of the UCSD CCNE, led the research team that developed what it calls a logic-based nanoparticulate system for detecting multiple cancer biomarkers. The researchers published their results in the Journal of the American Chemical Society. The investigators built their system using superparamagnetic nanoparticles that they first coated with either avidin or biotin, two biomolecules that bind to one another with legendary specificity and avidity. Then, to keep these nanoparticles from Wbinding to each other through their new biotin or avidin coatings, the investigators added one of two different protein-polymer constructions. Both constructions consisted of a short segment of protein linked to a long stretch of poly(ethylene glycol) (PEG); in one case, the protein segment was a substrate for an enzyme known as MMP2, in the other case, the protein was a substrate for the enzyme MMP7. MMP2 is overexpressed in many types of cancer, particularly metastatic disease, whereas MMP7 may be involved in the early stages of breast cancer development. Tests showed that only these specific enzymes were able to cleave their specific protein substrates, releasing the PEG layer from the nanoparticles... Whole on "nanotechwire":[ http://www.nanotechwire.com]

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