Quantum dot-doped silica nanoparticles as probes for targeting of T-lymphocytes

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 (αCD3). 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.

[1]  T. Mustelin,et al.  Full-length single-walled carbon nanotubes decorated with streptavidin-conjugated quantum dots as multivalent intracellular fluorescent nanoprobes. , 2006, Biomacromolecules.

[2]  Stefano Bellucci,et al.  Synthesis and characterization of supramolecular nanostructures of carbon nanotubes and ruthenium-complex Luminophores. , 2006, Journal of nanoscience and nanotechnology.

[3]  A Paul Alivisatos,et al.  Cellular effect of high doses of silica-coated quantum dot profiled with high throughput gene expression analysis and high content cellomics measurements. , 2006, Nano letters.

[4]  Yang-Wei Lin,et al.  Synthesis and properties of water-soluble core-shell-shell silica-CdSe/CdS-silica nanoparticles. , 2006, Journal of Nanoscience and Nanotechnology.

[5]  Charles DiMarzio,et al.  Surface functionalization of gold nanoparticles using hetero-bifunctional poly(ethylene glycol) spacer for intracellular tracking and delivery , 2006, International journal of nanomedicine.

[6]  Ron C. Hardman A Toxicologic Review of Quantum Dots: Toxicity Depends on Physicochemical and Environmental Factors , 2005, Environmental health perspectives.

[7]  Yuejin Zhu,et al.  Synthesis of SiO2-coated ZnMnFe2O4 nanospheres with improved magnetic properties. , 2005, Journal of nanoscience and nanotechnology.

[8]  H. Dai,et al.  Carbon nanotubes as intracellular protein transporters: generality and biological functionality. , 2005, Journal of the American Chemical Society.

[9]  Alberto Bianco,et al.  Carbon nanotubes for the delivery of therapeutic molecules , 2004, Expert opinion on drug delivery.

[10]  Weihong Tan,et al.  Optimization of dye-doped silica nanoparticles prepared using a reverse microemulsion method. , 2004, Langmuir : the ACS journal of surfaces and colloids.

[11]  R. Langer,et al.  Designing materials for biology and medicine , 2004, Nature.

[12]  R. Haag,et al.  Supramolecular drug-delivery systems based on polymeric core-shell architectures. , 2004, Angewandte Chemie.

[13]  K. Leong,et al.  Multifunctional nanorods for gene delivery , 2003, Nature materials.

[14]  Erkki Ruoslahti,et al.  Nanocrystal targeting in vivo , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[15]  M. Wilchek,et al.  Biotin binding changes the conformation and decreases tryptophan accessibility of streptavidin , 1990, Journal of protein chemistry.