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Collaborators:
E. Angert, B. Baird, C. Batt, E. Giannelis, D. Sogah
Program Objectives The following areas are being actively explored: (1) Macromolecular synthesis and characterization of nanoscale functionalized biocompatible polymers that are specific to antibodies and immune receptors on cells for use in controlling receptor-mediated cell activation and eventual application in biosensors; (2) engineering of controlled arrays of bioactive groups on surfaces for probing biological systems and detecting biomolecules in complex media; (3) the use of S-layer proteins as templates for protein nanostructures and particles on length scales only accessible by nanotechnology, and (4) biological interfacing of engineered nanobiohybrids as novel gene and drug delivery systems. Accomplishments We have fabricated arrays of nanoparticles containing dinitrophenyl for IgE binding, pyrene for optical studies, biotin for streptavidin interactions and many organic functional groups using our proprietary nitroxide exchange chemistry. We extended the concept to functionalization of magnetic nanoparticles, which retained their superparamagnetic properties with potential for use in magnetic imaging of cells. We have developed biocompatible nanohybrid materials that are effective in increasing the solubility and bioavailability of water-insoluble drugs, such as camptothecin, taxol® and a new anti-inflammatory drug. We demonstrated delivery and expression of a full transgene, synthesized for the first time Gd-containing nanoparticle cores for MRI and successfully administered nanohybrids in cell culture and living mice. Future Directions We plan to develop the enabling technology for molecular level understanding of the factors affecting biological interactions on surfaces for applications in magnetic imaging, biosensing, and drug delivery. We will synthesize trivalently labeled DNP three armed (or Y shaped) synthetic systems whose nanoscale dimensions will be adjusted by controlling the length of the arms of the Y-shaped polymer. Using our immobilized enzyme-catalyzed polymer synthesis, we will build simple microfluidic structures for in situ polymer fabrication. Their performance and the ability of the polymers to be thermo-responsive will be tested. In addition, we will construct a model device with an imbedded polymeric valve and filtration. We will extend our biofunctionalization technology to nanoparticles and carbon nanotubes and develop techniques for introducing a single bioactive group per particle in order to probe more precisely the receptor binding. We will design S-layer proteins to allow the post-translational attachment of site-specific chemistries, develop photolithographic methods to pattern photoactive S-layers and attach and test FETs on the S-layer scaffold surface. We will design, synthesize, and evaluate the biological efficacy of nanohybrids as cancer diagnostics and therapeutics in cell lines and primary cell cultures. The nanohybrids will also be evaluated in targeting, imaging and reporting applications and in animal models. |
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