title: Quantum dot-doped silica nanoparticles as probes for targeting of T-lymphocytes.
abstract: To enhance diagnostic or therapeutic efficacy, novel nanomaterials must be engineered to function in biologically relevant environments, be visible by conventional fluorescent microscopy, and have multivalent loading capacity for easy detection or effective drug delivery. Here we report the fabrication of silica nanoparticles doped with quantum dots and superficially functionalized with amino and phosphonate groups. The amino groups were acylated with a water-soluble biotin-labeling reagent. The biotinylated nanoparticles were subsequently decorated with neutravidin by exploiting the strong affinity between neutravidin and biotin. The resultant neutravidin-decorated fluorescent silica nanoparticles stably dispersed under physiological conditions, were visible by conventional optical and confocal fluorescent microscopy, and could be further functionalized with macromolecules, nucleic acids, and polymers. We also coated the surface of the nanoparticles with biotinylated mouse anti-human CD3 (alphaCD3). The resultant fluorescent nanoassembly was taken up by Jurkat T cells through receptor-mediated endocytosis and was partially released to lysosomes. Thus, quantum dot-doped silica nanoparticles decorated with neutravidin represent a potentially excellent scaffold for constructing specific intracellular nanoprobes and transporters.
authors.affiliation: Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA. mbottini@burnham.org
authors.forename: Massimo
authors.initials: M
authors.lastname: Bottini
authors.forename: Federica
authors.initials: F
authors.lastname: D'Annibale
authors.forename: Andrea
authors.initials: A
authors.lastname: Magrini
authors.forename: Fabio
authors.initials: F
authors.lastname: Cerignoli
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Arimura
authors.forename: Marcia I
authors.initials: MI
authors.lastname: Dawson
authors.forename: Enrico
authors.initials: E
authors.lastname: Bergamaschi
authors.forename: Nicola
authors.initials: N
authors.lastname: Rosato
authors.forename: Antonio
authors.initials: A
authors.lastname: Bergamaschi
authors.forename: Tomas
authors.initials: T
authors.lastname: Mustelin
mesh_terms: D000818:Animals; D001360:Avidin / Q000737:chemistry* / Q000276:immunology; D002478:Cells, Cultured; D016503:Drug Delivery Systems / Q000379:methods*; D004705:Endocytosis / Q000502:physiology*; D051379:Mice; D008856:Microscopy, Fluorescence / Q000379:methods*; D015336:Molecular Probe Techniques; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D045663:Quantum Dots; D012822:Silicon Dioxide / Q000737:chemistry; D013050:Spectrometry, Fluorescence / Q000379:methods; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
chemical_list: C093483:neutravidin; D001360:Avidin; D012822:Silicon Dioxide