Citrate-stabilized lanthanide-doped nanoparticles: brain penetration and interaction with immune cells and neurons.
OBJECTIVE
To unravel key aspects of the use of lanthanide-doped nanoparticles (NPs) in biomedicine, the interaction with immune and brain cells.


METHODS
Effects of citrate-stabilized CaF2and SrF2: Yb, Er NPs (13-15 nm) on human dendritic cells and neurons were assessed in vitro. In vivo distribution was analyzed in mice at tissue and ultrastructural levels, and with glia immunophenotyping.


RESULTS
The NPs did not elicit dendritic cell activation and were internalized by cultured neurons, without viability changes. After intravenous injection, NPs were found in the brain parenchyma, without features of glial neuroinflammatory response.


CONCLUSIONS
Lanthanide-doped NPs do not activate cells protagonists of systemic and brain immune responses, are endocytosed by neurons and can cross an intact blood-brain barrier.
Department of Neuroscience, Biomedicine & Movement Sciences, University of Verona, Verona, Italy.
Corinne
C
Portioli
Department of Biotechnology, University of Verona, Verona, Italy.
Marco
M
Pedroni
Department of Neuroscience, Biomedicine & Movement Sciences, University of Verona, Verona, Italy.
Donatella
D
Benati
Department of Medicine, University of Verona, Verona, Italy.
Marta
M
Donini
Department of Neuroscience, Biomedicine & Movement Sciences, University of Verona, Verona, Italy.
Roberta
R
Bonafede
Department of Neuroscience, Biomedicine & Movement Sciences, University of Verona, Verona, Italy.
Raffaella
R
Mariotti
Department of Diagnostics & Public Health, University of Verona, Verona, Italy.
Luigi
L
Perbellini
Department of Diagnostics & Public Health, University of Verona, Verona, Italy.
Marzia
M
Cerpelloni
Department of Medicine, University of Verona, Verona, Italy.
Stefano
S
Dusi
Department of Biotechnology, University of Verona, Verona, Italy.
Adolfo
A
Speghini
Department of Neuroscience, Biomedicine & Movement Sciences, University of Verona, Verona, Italy.
Marina
M
Bentivoglio
D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging* / Q000276:immunology; D002124:Calcium Fluoride / Q000737:chemistry; D002470:Cell Survival; D002478:Cells, Cultured; D019343:Citric Acid / Q000737:chemistry*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D004705:Endocytosis; D005063:Europium / Q000737:chemistry; D006801:Humans; D028581:Lanthanoid Series Elements / Q000737:chemistry*; D008297:Male; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009457:Neuroglia / Q000276:immunology / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D061848:Optical Imaging; D010316:Particle Size; D010539:Permeability; D013324:Strontium / Q000737:chemistry; D014018:Tissue Distribution; D015018:Ytterbium / Q000737:chemistry
D028581:Lanthanoid Series Elements; D019343:Citric Acid; D005063:Europium; D015018:Ytterbium; D002124:Calcium Fluoride; D013324:Strontium
biodistribution; bioimaging; blood–brain barrier; cytokines; dendritic cells; endocytosis; glia; immune response; lanthanide-doped nanoparticles