Nontoxic Si Nanoprobes for Mulitple Biomarker Imaging

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DESCRIPTION (provided by applicant): Plaque composition is an important assessment point in the prevention of acute coronary syndrome. More so than plaque size, the composition of a plaque and presence of specific markers indicate if a plaque is at risk for rupture. Rupture can lead to thrombotic events that cause mortality or morbidity. A number of plaque components have been identified that correlate with plaque stability, including cell types and cytokines associated with inflammation, but these are difficult to study in vivo. In addition, no single marker is an absolute predictor for plaque risk to rupture clinicians are increasingly interested in multiple marker assessment. Therefore a need exists for imaging methods that will allow for clinical assessment of many plaque components. Noninvasive methods such as magnetic resonance imaging (MRI) and positron emission tomography (PET) are capable of imaging marker expression using targeted contrast agents, but multiple markers cannot be assessed simultaneously. If a clinician is interested to examine more than one marker, studies must be done serially, with a wait time in between for the previous targeted contrast agent to clear (for MRI), or decay (for PET). The overall goal of this proposal is to develop synthetic methods and conduct imaging studies leading toward the use of nontoxic, semiconductor, nanoparticle, imaging probes (quantum dots, QDs) in the management of human coronary artery disease. We propose to develop silicon QDs that are luminescent and also paramagnetic to allow both optical and MR imaging. Unlike traditional cadmium based QDs, silicon nanoparticles have the promise to be nontoxic as even free silicon relatively nontoxic. The QDs can be targeted to identify specific biomarkers important in cardiovascular preventative medicine and both magnetic resonance and optical imaging are then employed to assess plaque composition--MRI is used to detect regions where biomarkers are expressed, while optical methods are employed to interrogate these regions to identify the types of biomarkers present. In this proposal we describe methods to synthesize Si QDs of specific size and imaging properties, characterize the toxicity and uptake of these nanoparticles in cell cultures, and demonstrate the utility for these QDs to label multiple biomarkers of plaque stability in an animal model. The proposed work develops a new imaging material that would allow physicians to assess whether an arterial plaque was at risk to rupture. Plaque rupture is a graver threat to health than the size of the plaque. The physician can use this information to decide on treatment plans for the patient and to identify plaques that need to be more carefully monitored.