The idea of making biocompatible multifunctional nanoparticles, combining therapy, imaging and targeting, was aimed at cancer from the start a dozen years ago. This presentation will emphasize targeted theranostic nanoparticles, where “theranostic” literally means combining therapy and diagnostics, but more generally may mean a combination of imaging/visualization with therapy/surgery. Specific examples will cover (1) imaging (MRI, CT and optical methods), (2) therapy (chemo, photodynamic, radiation) and (3) guided surgery (using intra-operative imaging and therapy). Progress on brain and on head and neck cancer will be reported.

Nanoparticles consisting of different biocompatible materials are attracting a lot of interest in the biomedical area as useful tools for drug delivery, photo-therapy and contrast enhancement agents in MRI, fluorescence and confocal microscopy. This work mainly focuses on the synthesis of polymeric/inorganic multifunctional nanoparticles (PIMN) based on biocompatible di-block copolymer poly(L,L-lactide-co-ethylene glycol) (PLLA-PEG) via an emulsion-evaporation method. Besides containing a hydrophobic drug (Indomethacin), these polymeric nanoparticles incorporate different visualization agents such as superparamagnetic iron oxide nanoparticles (SPION) and fluorescent Quantum Dots (QDs) that are used as contrast agents for Magnetic Resonance Imaging (MRI) and fluorescence microscopy together. Gold Nanorods are also incorporated in such nanostructures to allow simultaneous visualization and photodynamic therapy. MRI studies are performed with different loading of SPION into PIMN, showing an enhancement in T2 contrast superior to commercial contrast agents. Core-shell QDs absorption and emission spectra are recorded before and after their loading into PIMN. With these polymeric/inorganic multifunctional nanoparticles, both MRI visualization and confocal fluorescence microscopy studies can be performed. Gold nanorods are also synthesized and incorporated into PIMN without changing their longitudinal absorption peak usable for lased excitation and phototherapy. In-vitro cytotoxicity studies have also been performed to confirm the low cytotoxicity of PIMN for further in-vivo studies.

The Lectin-Carbohydrate interaction was investigated by combining the Quartz Crystal Microbalance-QCM technique with signal amplifying biomimetic nanoparticle-NP platforms. A library of glyconanoparticles was prepared and the avidity of these NPs for immobilised lectin layers was then evaluated by a QCM setup. Large responses were observed as a result of surface recognition by nanoparticles displaying the appropriate molecular functionality. Large affinity enhancements were also in evidence due to the biomimetic nature of the glyconanoparticle assemblies' carbohydrate presentation demonstrating evidence of the cluster glycoside effect.

Biocompatible, water-soluble, green luminescent silicon quantum dots (SiQDs) were developed as transfection tool for small interfering RNA (siRNA). The research goal was to down-regulate via the RNA interference (RNAi) mechanism the P-glycoprotein expression of the multidrug resistant gene 1 (MDR1) in a human colon carcinoma cell line (Caco-2). The internalization of 2-vinylpyridine terminated SiQDs (2-vipySiQDs) by Caco-2 cells as observed in confocal laser scanning microscopy imaging studies occurs via endocytosis. Experiments employing agarose gel electrophoresis revealed that 2-vipySiQD-siRNA complexes are formed through electrostatic interactions. The release of siRNA in the cytosol with subsequently RNAi induced down-regulation of the P-glycoprotein translation was verified by detecting a reduced ABCB1 mRNA level in transfected Caco-2 cells employing real-time PCR. Additional evidence for successful ABCB1 gene silencing was obtained by measuring a significant decrease of the P-glycoprotein transporter efficiency for the fluorescent substrate Rhodamine 123 (Rh123).

In the present study pure and doped gallium nitride (GaN) nanocrystals were synthesized using gallium trichloride (GaCl3), ethylene diamine tetra acetic acid (EDTA) and cobalt chloride as raw materials at a temperature of 900 °C in ammonia (NH3) atmosphere. The XRD spectrum for pure and cobalt doped GaN nanocrystals shows the formation of single phase wurtzite structure. No impurity phases were observed in the X-ray diffraction pattern for 5% Co doped sample whereas secondary phases were observed when the doping concentration exceeds 5 %. Shift in X-ray diffraction peaks were observed in Co doped samples towards lower angle side compared to pure GaN, it confirms that the Co atoms introduces in to the GaN lattice. Transmission electron microscopy images were taken for pure and Co doped GaN. Hexagonal morphology was observed in pure GaN samples. The average size of the particle was found to be ˜20 nm for pure and Co doped GaN. The magnetic measurements were carried out for the Co (5% & 10%) doped samples both at 10K and 300K. Clear hysteresis loop in the magnetization curve suggest the presence of ferromagnetic behavior in cobalt doped GaN. Temperature dependent magnetization (M-T) measurements were also carried out for doped samples using Super Conducting Quantum Interface Device (SQUID) from 10K to 300K The results have been discussed and correlated to structural and magnetic properties of the materials.

We report on high transversal relaxivity values of composite iron oxide-silica nanoparticles. To obtain the material, pre-formed maghemite nanoparticles were coated with silica by sol-gel chemistry, using supercritical fluids as the reaction media. The composite particles were monodisperse and consisted of a core of several maghemite nanoparticles, surrounded by a thick silica shell. The high pressure and high temperature process did not affect the iron oxide particle size but induced an increase on their saturation magnetization values, possibly due to an improvement of the particle crystallinity. These iron oxide-based materials present very high transversal relaxivity values which can be correlated to the magnetic moment and to the silica shell width of the composite particles. Moreover, composite particles are not cytotoxic and they are dispersable in polar solvents.

Light emission from Si nanocrystals ( SiNCs ) embedded in Si oxide was studied in this work. SiNCs were fabricated by annealing a Si-rich oxide ( SRO ) deposited by a plasma-enhanced chemical vapor deposition ( PECVD ) system. The gas flow ratio between SiH4 and N2O of a precursor gas was changed by varying a N2O gas flow rate and the annealing temperature was varied from 800 to 1100°C. The highest PL intensity was obtained with a N2O flow rate of 125sccm, a SiH4 flow rate of 1400sccm and annealing temperature of 900°C. The PL wavelength was also controlled by N2O gas flow rate and annealing temperature, with blue shifting to the visible wavelengths for increasing N2O flow rate and decreasing annealing temperature. In addition, forming gas ( 4% H2 ) anneal for 1 hour, which is a common method to passivate Si surface, at 500°C to SiNCs was used to further enhance the emission intensity. To approach emission at shorter wavelength, the Si oxide with SiNCs / SiO2 multi layer structure ( MLS ) was also fabricated by similar methods. The SiO2 layer was used as a diffusion barrier to extra Si on vertical direction during the annealing process. Such a barrier can effectively reduce the diameter of SiNCs and shift the emission peak to shorter wavelength. A blue shift from PL was clearly observed as the thickness of Si oxide layer with SiNCs in MLS reduces. Finally, the PIN light emitting diode which consisted of n-type poly-Si / Si oxide with SiNCs / p-type poly-Si structure was also fabricated to study the electroluminescence ( EL ) of SiNCs. The current under the forward bias was about 10 times higher than under the reverse bias. The carrier injection mechanism assumed that Poole-Frenkel type conduction or hopping conduction dominates under a low electric field and Fowler-Nordheim tunneling dominates under a high electric field. EL was obtained with a forward bias voltage of around 6V and EL emission efficiency was proportional to the current density.

A combination of silver and gold is demonstrated in nanoscale objects. Silver and gold have similar but distinct chemical and physical properties. We employed three main chemistry related to silver and gold – underpotential deposition, epitaxial growth, and Galvanic replacement. Selective underpotential deposition of silver guided the growth direction of gold and generated gold octahedrons, cuboctahedrons, cubes, and rods. Epitaxial growth of silver on gold decahedral seeds formed silver-gold-silver heterometallic nanorods and wires. Galvanic replacement of silver for gold yielded asymmetric single hollow and symmetric double hollow structures. All silver/gold nanostructures exhibited characteristic optical features in the UV-vis-NIR ranges. Such structural variation and corresponding optical properties are useful for diverse applications in electronics, photonics, biology, and catalysis.

The complementary physical properties of the distinct constituents render polymer-grafted nanocrystals (PGNPs) intriguing materials systems in which property characteristics can be tuned over a wide range from hard particulate to soft polymer-type. Here we demonstrate that dependent on the molecular weight and the graft density of the grafted polymer chains, three characteristic regimes of PGNPs are observed: (1) hard-sphere type colloidal crystalline with the formation of cracks driven by short-range interactions, (2) plastic mesocrystalline with the crazing behaviors by chain entanglement, or (3) disordered structure with soft-polymer type interactions. In addition to controlling the mechanical properties of PGNPs, grafted chains can have a key role in mediating their gradual transformation into more ordered microstructures from nanoparticles with energetically unfavorable property (i.e., activation barrier for crystallization induced by polydisperse nanoparticles [1, 2]).

Active nanostructures which provide unique transformations are being introduced to phase matched porous silicon (PS) nano/micropores to form a platform for low power consumption highly selective sensors and microreactors. TiO2-xNx photocatalysts have been formed in seconds at room temperature at the nanoscale via the direct nitration of anatase TiO2 nanocolloids. Tunability throughout the visible depends upon the degree of agglomeration and the ability to seed these nanoparticles with metal ions. Co metal ion seeding leads to the efficient room temperature phase transformation, of anatase to rutile TiO2, where normally much higher temperatures are required. Seeding of a properly nitridated TiO2 nanocolloid with transition metal ions (Co, Ni) allows for the enhancement of the infrared spectra of the TiO2-xNx nitridated titania surface in excess of 10-fold, providing a means to analyze for minor contaminants and intermediates. Evidence for nitrogen fixation is found in Fe treated systems. The TiO2-xNx systems act as visible light absorbing photocatalyts. These photocatalysts and additional nanostructured metal oxides can be placed on the surface of PS-based sensor and microreactor configurations to greatly improve the interface response.

The photoluminescence spectra and its homogeneity for InAs quantum dots (QDs) embedded into In0.15Ga0.85As/GaAs quantum well (QW) structures with QDs grown at different temperatures (470-535°C) have been investigated at 300 K. Photoluminescence (PL) spectra along the scanning line crossed the wafers were measured at 300 K in a set of points on the QD structures under the excitation of the 804 nm line of a solid state IR laser at an excitation power density of 100 W/cm2. In QD structures with InAs QDs grown at 470°C the low integrated PL intensity, the high dispersion of QD sizes in ensemble and, as a result, the large value of FWHM (50-70meV), but the low dispersion of QD ensemble parameters along the line crossed the structures have been detected. In QD structures grown at high temperatures 490-535 °C the high integrated PL intensity, the low dispersion of QD sizes in ensemble and, as a result, less values of FWHM, but the essential dispersion of QD ensemble parameters along the line crossed the structures have been revealed. The reasons of these types of PL nonhomogeneity have been discussed.

Here we present a study on the polypropylene/montmorillonite interaction based on x-ray diffraction, transmission electron microscopy (TEM) and scanning transmission x-ray microscopy (STXM) measurements, which provides a complete picture of the intercalation and exfoliation processes taking place.

Quantum Dots (QDs) bound to gold nanoparticles have shown photoluminescence (PL) quenching dependent on distance between the two particles. The incident light from the QD couples to plasmon excitation of the metal when the frequencies of the light and the surface plasmon resonance (SPR) coincide, leading to a reduction in emitted PL in the system. The quenching effect of gold nanoparticles on QDs was used to study protein-protein interactions with the potential for drug screening applications. CdTe and CdHgTe QDs with emission wavelengths from 500˜900nm were synthesized and gold nanospheres and nanorods with controlled absorption in the visible and near-infrared (NIR) wavelength regions were prepared. The PL quenching of QD-Protein-Protein-Au complexes was studied as a function of Au concentration, QD size and protein type. A quenching efficiency of up to 90% was observed. The QD-Au complexes were also studied for electric potential sensing. The surface of the QDs was negatively charged due to thiol ligands capping. By applying a positive potential on the gold or gold nanoparticle attached substrate, the local electric field between the substrate and the statically charged QDs would pull the QDs closer to the gold surface and quench the QD PL. PL quenching of QD with Au was studied as a function of electric signal and QD type. In this methodology, electric signals were effectively converted to optical signals.

Fabrication of transparent, conductive phase-segregated ITO/PC composites was accomplished by compression molding of dry mixed constituents. Mixtures of 50nm indium tin oxide particles in a polycarbonate matrix of compositions ranging from phr = 1.0 to 0.001 were measured by optical and electrical methods. Measured transmittance ranged from 5% to 68% at 400nm, 15% to 80% at 700nm, and averaged 10% to 75% across the visible spectrum. Resistance was measured by impedance spectroscopy. Resistivities of the different composites spanned 10 orders of magnitude. Electrical percolation was found to occur near phr = 0.15.

A novel system has been developed to catalyze reactions at the oil/water interface of a biphasic liquid system. Stabilization of emulsions was accomplished through the use of nanohybrids composed of hydrophilic oxide particles and hydrophobic Single-Walled Carbon Nanotubes (SWNT), generated in the CoMoCAT process. These nanohybrids are inherently amphiphilic, and tend to adsorb at the interface of a biphasic water/oil liquid system. When enough energy is added to the system, these particles stabilize emulsions by suppressing the coalescence of the droplets and increasing the viscoelastic or pseudoplastic character of the liquid film between droplets. , Depending on contact angle of the particles at the liquid-liquid interface it was possible to stabilize water-in-oil or oil-in-water emulsions. The resulting emulsions are remarkably stable against coalescence and sedimentation, and can be easily separated by filtration or centrifugation, which make them suitable for applications in interfacial catalytic processes in which the catalyst can be easily recovered after reaction. Catalytic activity was imparted by transition metal clusters supported onto the nanohybrids. These metals selectively catalyze reactions at the Oil/Water interface. The proof-of-concept of the biphasic hydrogenation and condensation catalysis was obtained with three reactions of interest in biorefining. The first example was the hydrodeoxygenation of vanillin (4-hydroxy-3-methoxybenzaldehyde). The second example was the conversion of molecules that were exclusively soluble in the aqueous or the organic phase, like glutaraldehyde (water phase) and octanal (oil phase). In the third example we explored a tandem reaction sequence in which Pd-catalyzed hydrogenation was paired with a preceding Aldol-condensation of 5- methylfurfural and acetone. It was demonstrated that with these nanohybrids it is possible to selectively accomplish hydrodeoxygenation and condensation reactions at the water/oil interface of a biphasic system, followed by migration of the products to the oil phase. This contribution provides a proof-of-concept for a promising catalytic system with many potential applications in the liquid phase, such as bio-oil upgrading, production of specialty chemicals, and pharmaceutical applications in which selective reaction and product separations, based on water solubility can be desirable.

Electrical conduction of metal nanoclusters by percolation is a very interesting area in nano-device. For more functional nano-sensors consisting of multiple nanocluster blending film, various metals, such as Cu and Ni nanocluster films were fabricated using inert-gas condensation method. The percolation threshold of the films was measured. In addition, for the operation of sensors using these nanocluster films in air, aging experiments of the percolated films in air were carried out. While the percolation threshold was in connection not with the material species but with the area coverage of nanocluster films, the conductive characteristics according to the aging temperature depended on the material species. Reversible and irreversible conduction behaviors of nanocluster films were investigated with nanoscale microstructures using electron microscopes.

The use of nanoparticles as carriers of photosensitizer (PS) molecules for photodynamic therapy (PDT) has attracted much interest on core-shell nanosize structures. Herein, we used a simple aqueous solution method to synthesize Fe3O4/ZnO core-shell nanoparticles. X-ray diffraction (XRD) analyses showed the presence of well defined peaks corresponding to Fe3O4 and ZnO in as-synthesized nanocrystals. Vibrating sample magnetometer (VSM) measurements showed that these nanoparticles exhibited superparamagnetic behavior of the core with no coercivity nor remanence. X-ray photoelectron spectroscopy (XPS) analyses revealed the presence of Zn1/2 and Zn3/2 species on the surface of nanocrystals. Photoluminescence measurements showed excitonic emission of ZnO co-existing with a weak and broad defect- related green emission at room temperature. The generation of singlet oxygen was monitored via the photooxidation of diphenyl-1,3-isobenzofuran (DPBF) with different light sources, followed by absorption spectroscopy at 409 nm. The capability of synthesized nanoparticles to generate singlet oxygen has also been verified.