title: Insight on the fate of CNS-targeted nanoparticles. Part I: Rab5-dependent cell-specific uptake and distribution.
abstract: Nanocarriers can be useful tools for delivering drugs to the central nervous system (CNS). Their distribution within the brain and their interaction with CNS cells must be assessed accurately before they can be proposed for therapeutic use. In this paper, we investigated these issues by employing poly-lactide-co-glycolide nanoparticles (NPs) specifically engineered with a glycopeptide (g7) conferring to NPs the ability to cross the blood brain barrier (BBB) at a concentration of up to 10% of the injected dose. g7-NPs display increased in vitro uptake in neurons and glial cells. Our results show that in vivo administration of g7-NPs leads to a region- and cell type-specific enrichment of NPs within the brain. We provide evidence that g7-NPs are endocytosed in a clathrin-dependent manner and transported into a specific subset of early endosomes positive for Rab5 in vitro and in vivo. The differential Rab5 expression level is strictly correlated with the amount of g7-NP accumulation. These findings show that g7-NPs can cross the BBB and target specific brain cell populations, suggesting that these NPs can be promising carriers for the treatment of neuropsychiatric and neurodegenerative diseases.
authors: Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors: Antonietta
authors: A
authors: Vilella
authors: Pharmaceutical Technology, Te.Far.T.I. group, Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors: Giovanni
authors: G
authors: Tosi
authors: WG Molecular Analysis of Synaptopathies, Neurology Dept., Neurocenter of Ulm University, Ulm, Germany; Institute for Anatomy and Cell Biology, Ulm University, Ulm, Germany.
authors: Andreas M
authors: AM
authors: Grabrucker
authors: Pharmaceutical Technology, Te.Far.T.I. group, Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors: Barbara
authors: B
authors: Ruozi
authors: Pharmaceutical Technology, Te.Far.T.I. group, Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors: Daniela
authors: D
authors: Belletti
authors: Pharmaceutical Technology, Te.Far.T.I. group, Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors: Maria Angela
authors: MA
authors: Vandelli
authors: Institute for Anatomy and Cell Biology, Ulm University, Ulm, Germany.
authors: Tobias M
authors: TM
authors: Boeckers
authors: Pharmaceutical Technology, Te.Far.T.I. group, Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors: Flavio
authors: F
authors: Forni
authors: Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy. Electronic address: michele.zoli@unimore.it.
authors: Michele
authors: M
authors: Zoli
mesh_terms: D000818:Animals; D001692:Biological Transport; D001921:Brain / Q000378:metabolism*; D002478:Cells, Cultured; D004705:Endocytosis; D006020:Glycopeptides / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D019344:Lactic Acid / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D020696:rab5 GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D006020:Glycopeptides; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D020696:rab5 GTP-Binding Proteins
keywords: CNS targeting; Distribution; Nanoparticles; Neuronal uptake