Quantum dot-doped silica nanoparticles as probes for targeting of T-lymphocytes
Massimo Bottini1,2,4, Federica D’Annibale2, Andrea Magrini2, Fabio Cerignoli1, Yutaka Arimura1, Marcia I Dawson1, Enrico Bergamaschi5, Nicola Rosato3, Antonio Bergamaschi1, Tomas Mustelin1
1Burnham Institute for Medical Research, La Jolla, CA, USA; 2NAST and Department of Environmental, Occupational and Social Medicine, University of Rome Tor Vergata, Rome, Italy; 3NAST and Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, Rome, Italy; 4INFN, Laboratori Nazionali di Frascati, Frascati, Italy; 5Department of Clinical Medicine, Nephrology and Health Sciences, University of Parma, Parma, Italy
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 (αCD3). The resultant fluorescent nanoassembly was taken up by Jurkat T cells through receptor-mediated endocytosis and was partially released to lysosomes. Thus, quantum dotdoped silica nanoparticles decorated with neutravidin represent a potentially excellent scaffold for constructing specific intracellular nanoprobes and transporters.
Keywords: silica nanoparticles, neutravidin, surface functionalization, endocytosis, intracellular nanoprobe