We describe the preparation of monodisperse, lanthanide-doped hexagonal-phase NaYF4 upconverting luminescent nanoparticles for protein conjugation. Their core was coated with a silica shell which then was modified with a poly(ethylene glycol) spacer and N-hydroxysuccinimide ester groups. The nanoparticles were characterized by transmission electron microscopy, Raman spectroscopy, X-ray diffraction, and dynamic light scattering. The N-hydroxysuccinimide ester functionalization renders them highly reactive towards amine nucleophiles (e.g., proteins). We show that such particles can be conjugated to proteins. The protein-reactive UCLNPs and their conjugates to streptavidin and bovine serum albumin display multicolor emissions upon 980-nm continuous wave laser excitation. Surface plasmon resonance studies were carried out to prove bioconjugation and to compare the affinity of the particles for proteins immobilized on a thin gold film.
Magnetic optical sensor particles with multifunctional cores and shells are synthesized via a facile nanoprecipitation method and the subsequent modification of the particle shell. The hydrophobic particle core includes optical oxygen indicators, a light harvesting system, photosensitizers, and magnetic nanoparticles. Further functionalities are introduced by modifying the shell with enzymes, antibodies, multiple layers of polyelectrolytes, stimuli‐responsive polymers, and luminescent indicator dyes. The hydrodynamic diameter is tunable by varying different precipitation parameters.
A collection of new reversible glycosidase inhibitors of the iminoalditol type featuring Nsubstituents containing perfluorinated regions has been prepared for evaluation of physicochemical, biochemical and diagnostic properties. The vast variety of feasible oligofluoro moieties allows for modular approaches to customised structures according to the intended applications, which are influenced by the fluorine content as well as the distance of the fluorous moiety from the ring nitrogen. The first examples, in particular in the D-galacto series, exhibited excellent inhibitory activities. A preliminary screen with two human cell lines showed that, at subinhibitory concentrations, they are powerful pharmacological chaperones enhancing the activities of the catalytically handicapped lysosomal D-galactosidase mutants associated with GM1 gangliosidosis and Morquio B disease.
Summary
N-Alkylation at the ring nitrogen of the D-galactosidase inhibitor 1-deoxygalactonojirimycin with a functionalised C6 alkyl chain followed by modification with different aromatic substituents provided lipophilic 1-deoxygalactonojirimycin derivatives which exhibit inhibitory properties against β-glycosidases from E. coli and Agrobacterium sp. as well as green coffee bean α-galactosidase. In preliminary studies, these compounds also showed potential as chemical chaperones for GM1-gangliosidosis related β-galactosidase mutants.
Oxygen sensing, magnetic, and upconversion luminescence properties are combined in multi-functional composite particles prepared herein by a simple mixing, baking, and grinding procedure. Upconverting nanocrystals are used as an excitation source and an oxygen indicator with far-red emission. The composite particles are excited with near infrared (NIR) laser light (980 nm). The visible upconversion emission is converted into an oxygen concentration-dependent far-red emission (<750 nm) using an inert mediator dye and a platinated benzoporphyrin dye. This concept combines the advantages of NIR excitation and far-red emissive indicator dyes, offering minimized auto-fluorescence and enhanced membrane permeability. Additional functionality is obtained by incorporating magnetic nanoparticles into the composite particles, which enables easy manipulation and separation of the particles by the application of an external magnetic field.
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