We focus on understanding, controlling and tailoring the interfaces between inorganic nanocrystals and biological (and non-biological) systems. This requires making progress on several tracks.
- Develop synthetic schemes to prepare an array of nanocrystals made of semiconductor (quantum dots, QDs), metallic gold as well as magnetic materials, with control over their size and composition. Synthesis often involves reacting organometallic precursors at high (or room) temperature. Characterization of the structure, physical, chemical and spectroscopic properties of these materials is carried out using techniques such as UV-Vis absorption, fluorescence, small and wide angle x-ray scattering/diffraction, and TEM.
- Develop surface-functionalization strategies that employ, for instance, ligand exchange using modular multifunctional ligands that we have developed in the past few years. In this design, mono- and bi-reactive tunable length polyethylene glycol (PEG) segment are appended at the end of the high affinity thiotic acid (TA) or its reduced form, dihydrolipoic acid (DHLA). To the other end of the PEG we attach a variety of functional groups. These will provide additional solubility and biocompatibility to nanoparticles capped with such ligands. We have already demonstrated this rationale for preparing several DHLA-PEG ligands functionalized with amine, carboxylate and biotin. These ligands have provided an array of QDs and Au nanoparticles that are hydrophilic and stable over a broad range of biological conditions. We are designing additional chemical routes to attach several new groups that can achieve specific functions. Our design also targets new means of enhancing the affinity of the ligand to the surface of the nanocrystals.
- Design reproducible and simple to implement coupling schemes to attach these nanoparticles to various biological and non-biologic molecules. Then employ the resulting bio-inorganic conjugates and other forms of molecular assemblies in targeted demonstrations; high relevance in biology has been one main focus lately. These hydrophilic nanocrystals either as or conjugated to bio-receptors are utilized to develop in vitro and in vivo assays. These assays probe a variety of specific processes that occur in solution, at the membrane of live cells, or inside cellular compartments. We investigate protein-protein interactions and protein trafficking inside the cytoplasmic compartments and across cellular membranes. Specific problems we are interested in exploring and developing include sensing of specific enzymes, intracellular uptake of nanoparticle-protein cargos, sensing of intracellular indicators, and probing intra-membrane processes (e.g., T cell interactions with the surface of target infected cells involved in immune reaction). We use simple analytical techniques such as fluorescence detection (steady-state and time-resolved, Fluorescence Resonance Energy Transfer (FRET) as well as other forms of short range interactions.
- We are also interested in developing nanoparticles as platforms for assembling other reactive systems and small molecules with specific properties. In these assemblies the nanoparticles can be a passive transport vehicle, a visualization tool or reactive center to drive interactions with the surrounding environment in which these assemblies are dispersed.
