The major goal of this application is to synthesize new ceramic nanoprobes for bio-imaging that are highly fluorescent, bio-compatible, non-toxic, and tunable. This will be accomplished through a cross-discipinary venture between: (i) a group of material scientists and chemists from Sandia National Laboratories (Sandia) who are new to the NIH but have proven expertise in nanoparticle synthesis and biofurctionalization and (ii) a group of NIH-funded cell biologists from the University of New Mexico's School of Medicine (UNM-SOM) who have expertise in imaging cell signaling and trafficking pathways. The Sandia chemistry group will work concurrently towards two goals: (i) the synthesis of luminescent ceramic nanoprobes and (ii) innovations in functionalization that will deliver these probes to desired cellular targets. Initial synthetic efforts will focus on generating analogs of naturally occurring fluorescent (NOF) minerals as well as developing tailor-made nanoparticles doped with lanthanide cations for enhanced fluorescence. A library of novel compounds and synthetic pathways previously developed in the Sandia laboratory for nanoparticle synthesis will provide a unique knowledge base to initiate the development of useful luminescent ceramic nanoprobes. Probe functionalization will rely on PEG-phospholipids that allow for further bio-conjugation with proteins, peptides, small organic molecules/ligands and also with poly(arginine)-based transporters for transmembrane delivery. The UNM biology group will provide bioma terials to assist in the functionalization of the nanoprobes and will image probe delivery and specificity for cellular targets using live cell multispectral confocal microscopy. Preliminary interdisciplinary studies have validated the basic approaches for the synthesis of NOF nanoprobes and the biodelivery and imaging of nanoparticles. Intensive work to optimize the design, delivery, and imaging of these new nanoprobes is expected to achieve the RFA's goal of """"""""increases in the sensitivity and specificity of molecular probes"""""""" for imaging. Results from this award will set the stage for in vivo studies whose goals will be: (i) to detect cancer sites, inflammation, and other disease processes and (ii) to deliver and release drugs at disease sites by further manipulation of the functionalization chemistry. All of the innovations uncovered during the preparation of these nanoprobes will be shared in order to benefit medical research applications beyond those proposed in this investigation.
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