Colloidal Upconverting Nanoparticle Systems for Integration in Targeting, Therapeutics and Imaging Applications

The synthesis and surface modification of sodium gadolinium fluoride (NaGdF4:Er3+/Tm3+, Yb3+) nanoparticles were investigated for potential integration in biological applications. These nanoparticles are poised to replace conventional fluorophores in targeting, imaging and therapeutic applications. The latter possess several shortcomings ranging from photobleaching to requirements for ultraviolet (UV) excitation. In contrast, these nanoparticles are optically robust and may be excited using a near infrared (NIR) light source, which can be converted to UV, visible or NIR light via upconversion. Near infrared light is advantageous as it offers greater tissue penetration depth relative to UV or visible light and does not harm cells. Colloidal upconverting nanoparticles were synthesized using thermal decomposition. Synthetic parameters such as reaction temperature (280-320 C), time (30-180 min) and precursor addition rates (0.5 2.5 mL/min) were used to tailor the nanoparticle morphology, crystal phase (cubic or hexagonal) and particle size (10-80 nm). Integration of these nanoparticles in biological applications requires dispersibility in aqueous media. Hence several strategies such as silica shell coating and ligand exchange were carried out to render the nanoparticles hydrophilic. Orthogonal surface functionalization with amino and azido silane reagents was carried out on silica coated nanoparticles allowing for surface decoration using a cancer targeting folic acid derivative and a cis-platinum precursor therapeutic agent. The folate derivative was functionalized to the nanoparticle surface using "click" chemistry via surface N3 groups, while the cis-platinum derivative formed a coordination bond with the surface NH2 groups in a one-pot, one-step approach. The nanoparticle system was tri modal with targeting, imaging and therapeutic capacities. These luminescent upconverting NaY(Gd)F4:Tm3+/Yb3+ nanoparticles were investigated as novel contrast agents in magnetic resonance imaging. Hydrophilic citrate capped colloidal nanoparticles showed strong T1 enhancement effects. Positive contrast enhancement was observed at Gd3+ host concentrations as low as 5 mol%. The 5 nm sized nanoparticles produced similar contrast enhancement to current clinical gadolinium chelates with the added advantage that toxic Gd3+ leaching is not a concern as the ions are tightly bound in the crystal. These nanoparticles have been developed into multimodal systems, which may be used in cancer diagnostic and therapeutic applications as well as in whole body magnetic and optical imaging

Cross-relaxation and energy transfer processes in praseodymium-doped gadolinium gallium garnet (Gd3Ga5O12:Pr3+) bulk and nanocrystalline systems

The luminescence properties of singly-doped Pr 3+ and Pr 3+ /Yb 3+ co-doped nanocrystalline gadolinium gallium garnet (GGG, Gd 3 Ga 5 O 12 ) are investigated. Dominant blue/green emission emanating from the 3 P 0 [arrow right] 3 H 4 and 3 P 0 [arrow right] 3 H 6 transitions was observed after excitation using a wavelength of 457.9 nm. The luminescence properties of the nanocrystals were compared to the bulk material (single crystal) with identical Pr 3+ concentrations (1 mol%) and no noticeable shift in peak position was observed. Increasing the Pr 3+ concentration in the nanocrystals resulted in a decrease in 3Po and 3P, emission to lower lying states via the [ 3 P 0 , 3 H 4 ] [arrow right] [ 3 H 6 , 1 D 2 ] cross relaxation (CR) mechanism. Furthermore, a decrease in the 1 D 2 emission was observed and was attributed to the [ 1 D 2 , 3 H 4 ] [arrow right] [ 1 G 4 , 3 F 3,4 ] CR mechanism. The increase in CR efficiency was attributed to the smaller interionic distances between the dopant ions. Continuous wave excitation into the 1 D 2 level of the Pr 3+ ion at 606.9 nm transition produced blue upconversion luminescence. Based on the increase in transition lifetimes, an energy transfer (ET) upconversion mechanism was proposed. Furthermore, weak blue, green and red upconversion emission was observed from the 3 P 0 , 3 P 1 and 1 D 2 states following excitation into the 1 G 4 energy level with 980 nm. Upconversion was determined to primarily occur through excited state absorption. Co-doping the nanocrystalline GGG:Pr 3+ (1 mol%) samples with Yb 3+ (1-10 mol%) results in a 3-fold increase in upconversion emission intensity relative to the singly doped samples excited under the same conditions (n exc = 980 nm). The observed lifetimes obtained using 457.9 nm excitation suggest back transfer from the Pr 3+ ion to neighboring Yb 3+ ions which results in decrease in room temperature visible emission and upconversion luminescence

Carbon Dot-Sensitized Photoanodes for Visible Light-Driven Organic Transformations

Visible-light photosensitization of metal oxides to create heterostructures for the conversion of solar to chemical energy is a promising approach to produce solar fuels and other valuable chemicals. Carbon dots have recently been considered as suitable candidates to sensitize wide-band-gap metal oxide semiconductors due to their low cost and tunable optical properties. While photocatalytic systems using carbon dots as sensitizers have been reported, transformations involving the production of value-added chemicals as well as the electron transfer mechanisms underpinning photocatalysis within such heterostructures remain underexplored. Here, we report the sensitization of zinc oxide nanowires with carbon dots for the α-heteroarylation of 1-phenylpyrrolidine with 2-chlorobenzothiazole under visible-light illumination at room temperature. The carbon dots improve the light absorption of the nanowires in the visible region of the spectrum affording the use of white light to drive catalysis. From optical spectroscopy and electrochemistry investigations of the resulting nanohybrid material, the photocatalytic properties are explained by the band alignment at the zinc oxide–carbon dot junction where a series of single-electron transfers create the necessary potential to oxidize 1-phenylpyrrolidine. The resulting cascade of electron transfers into and from the carbon dots drives the α-heteroarylation to a 97% yield after 24 h

ZnAl hydrotalcites modified with nanocomposites nZVI–PAA for environmental remediation

Diffraction patterns of polyacrylic acid (PAA) encapsulated-(Fe)-modified ZnAl hydrotalcite (ZnAlH) showed the integration of Fe in the H lattice, resulting in a hybrid nanocomposite (Fe-PAA-ZnAlH), which was mainly verified with the characteristic shift in the 59–63° (2θ) region of the ZnAlH (110) reflection plane. The rise in the unit cell parameters (c and a) as the Fe % incremented, denoted incorporation of Fe in the ZnAlH red. Nonetheless, changes in the immobilizer molecular weight (PAA MW) from 1250 kDa to 5.1 kDa did not cause a difference in the distance between layers (c parameter) but in the cation-cation separation (a parameter), which meant that the nanoparticle was not located between layers, but in the lattice. The resulting band gap energies of the calcined hybrid nanocomposites were among 1.07–1.21 eV, which is an additional support of Fe+3 integration, suggesting insertion of Fe+3 3d orbitals between the valence and the conduction band of ZnO. Furthermore, nZVI were prepared through a pre-agglomeration reduction method, where COOH-groups were bound to metal cations. Initially, aqueous Fe+2 was bound to PAA [Fe+2-PAA], then reduced to obtain enclosed hybrid (nZVI-PAA). Less stability and more aggregation were observed with the lower molecular weight PAA. Additionally, PAA dissociation caused by pH changes affected the clustering of the nZVI particles. At higher MW, the hydrodynamic diameter and size distribution become smaller and tighter, respectively, allowing a more monodispersed population with sphere shape and organized in core–shell beads chains.Fil: Nieto Zambrano, Sorelis. Universidad de Guanajuato; MéxicoFil: Ramos Ramirez, Esthela. Universidad de Guanajuato; MéxicoFil: Tzompantzi Morales, Francisco. Universidad Autónoma Metropolitana; MéxicoFil: Boffito, Daria Camilla. No especifíca;Fil: Naccache, Rafik. Concordia University; CanadáFil: Gutiérrez Ortega, Norma L.. Universidad de Guanajuato; MéxicoFil: Litter, Marta Irene. Universidad Nacional de San Martín. Instituto de Investigación e Ingeniería Ambiental. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación e Ingeniería Ambiental; ArgentinaFil: Cipagauta Diaz, Sandra. Universidad Autónoma Metropolitana; MéxicoFil: Barbosa López, Aida Liliana. Universidad de Cartagena.; Colombi

High resolution fluorescence imaging of cancers using lanthanide ion-doped upconverting nanocrystals

During the last decade inorganic luminescent nanoparticles that emit visible light under near infrared (NIR) excitation (in the biological window) have played a relevant role for high resolution imaging of cancer. Indeed, semiconductor quantum dots (QDs) and metal nanoparticles, mostly gold nanorods (GNRs), are already commercially available for this purpose. In this work we review the role which is being played by a relatively new class of nanoparticles, based on lanthanide ion doped nanocrystals, to target and image cancer cells using upconversion fluorescence microscopy. These nanoparticles are insulating nanocrystals that are usually doped with small percentages of two different rare earth (lanthanide) ions: The excited donor ions (usually Yb3+ ion) that absorb the NIR excitation and the acceptor ions (usually Er3+, Ho3+ or Tm3+), that are responsible for the emitted visible (or also near infrared) radiation. The higher conversion efficiency of these nanoparticles in respect to those based on QDs and GNRs, as well as the almost independent excitation/emission properties from the particle size, make them particularly promising for fluorescence imaging. The different approaches of these novel nanoparticles devoted to "in vitro" and "in vivo" cancer imaging, selective targeting and treatment are examined in this reviewJ.A.C. is a Concordia University Research Chair in Nanoscience and is grateful to Concordia University for financial support of his research. J.A.C. and F.V. are grateful for financial support from the Natural Sciences and Engineering Research Council (NSERC) of Canada. R.N. is grateful for NSERC financial support through the Alexander Graham Bell Graduate Scholarship Program. B.F.Z. is grateful to les Fonds Québécois de Recherche sur la Nature et les Technologies (FQRNT) for financial support through the Graduate Scholarship Program. This work was also supported in part by the Universidad Autónoma de Madrid and Comunidad Autónoma de Madrid (Projects CCG087-UAM/MAT-4434 and S2009/MAT-1756), by the Spanish Ministerio de Educación y Ciencia (MAT 2010–16161). EMR acknowledges financial support from Fundación Alfonso Martín Escudero and Marie Curie IOF Fellowship Program (project 274404 LUNAMED

Nanoparticles for highly efficient multiphoton fluorescence bioimaging

In this paper, we demonstrate for the first time that the new class of fluoride-based inorganic upconverting nanoparticles, NaYF4:Er3+, Yb3+, are the most efficient multiphoton excited fluorescent nanoparticles developed to date. The near-infrared-to-visible conversion efficiency of the aforementioned nanoparticles surpasses that of CdSe quantum dots and gold nanorods, which are the commercially available inorganic fluorescent nanoprobes presently used for multiphoton fluorescence bioimaging. The results presented here open new perspectives for the implementation of fluorescence tomography by multiphoton fluorescence imaging

Elucidating the Quenching Mechanism in Carbon Dot-Metal Interactions–Designing Sensitive and Selective Optical Probes

Overexposure to metals has significant adverse effects on human and animal health coupled with nefarious consequences to the environment. Sensitive tools to measure low contaminant levels exist, but often come at a high cost and require tedious procedures. Thus, there exists a need for the development of affordable metal sensors that can offer high sensitivity and selectivity while being accessible on a global scale. Here, carbon dots, prepared in a one-pot synthesis using glutathione and formamide, have been developed as dual fluorescent metal sensing probes. Following extensive characterization of their physico-chemical properties, it is demonstrated that dual fluorescence can be exploited to build a robust ratiometric sensor with low-ppb detection sensitivity in water. This investigation shows that these optical probes are selective for Pb2+ and Hg2+ ions. Using steady-state and dynamic optical characterization techniques, coupled with hard and soft acid-base theory, the underlying reason for this selective behavior was identified. These findings shed light on the nature of metal-carbon dot interactions, which can be used to tailor their properties to target specific metal ions. Finally, these findings can be applicable to other fluorescent nanoparticle systems that are targeted for development as metal sensors

Carbon Dot Sensitized Photoanodes for Visible Light Driven Organic Transformations

Visible light photosensitization of metal oxides to create heterostructures for the conversion of solar-to-chemical energy is a promising approach to produce solar fuels and other valuable chemicals. Carbon dots have recently been considered as suitable candidates to sensitize wide bandgap metal oxide semiconductors due to their low cost and tunable optical properties. While photocatalytic systems using carbon dots as sensitizers have been reported, transformations involving the production of value-added chemicals as well as the electron transfer mechanisms underpinning photocatalysis within such heterostructures remain underexplored. Here we report the sensitization of zinc oxide nanowires with carbon dots for the α-heteroarylation of 1-phenylpyrrolidine with 2-chlorobenzothiazole under visible light illumination at room temperature. The carbon dots improve the light absorption of the nanowires in the visible region of the spectrum affording the use of white light to drive catalysis. From optical spectroscopy and electrochemistry investigations of the resulting nanohybrid material, the photocatalytic properties are explained by the band alignment at the zinc oxide-carbon dot junction where a series of single-electron transfers creates the necessary potential to oxidize 1-phenylpyrrolidine. The resulting cascade of electron transfers into and from the carbon dots drives the α-heteroarylation to a 97% yield after 24 hrs. <br /