title: Surface functionalisation regulates polyamidoamine dendrimer toxicity on blood-brain barrier cells and the modulation of key inflammatory receptors on microglia.
abstract: Dendrimers are branched polymers with spherical morphology. Their tuneable chemistry and surface modification make them valuable nanomaterials for biomedical applications. In view of possible dendrimer uses as brain-aimed nanocarriers, the authors studied amine- and lipid-functionalised (G4) polyamidoamine (PAMAM) biocompatibility with cell population forming the blood-brain barrier (BBB). Both amine-PAMAM and lipid-PAMAM dendrimers were able to enter endothelial and primary neural cells. However, only amine-PAMAM damaged cell membranes in a dose-dependent manner. Transmission electron microscopy evidenced the ability of dendrimers to precipitate salts and serum components present in culture medium that slightly increased toxicity of the amine-PAMAM. Amine- and lipid-PAMAM were both able to cross the BBB and differently induced CD11b and CCR2 overexpression on primary CX3CR1-GFP murine microglia in vitro. These data emphasise the role of dendrimer surface functionalisation in toxicity and neural immune cell activation, raising concerns about possible neuroinflammatory reactions.
authors.affiliation: Center for Nanotechnology Innovation @NEST, Istituto Italiano di Tecnologia , Piazza San Silvestro 12, Pisa , Italy.
authors.forename: Alice
authors.initials: A
authors.lastname: Bertero
authors.forename: Adriano
authors.initials: A
authors.lastname: Boni
authors.forename: Mauro
authors.initials: M
authors.lastname: Gemmi
authors.forename: Mariacristina
authors.initials: M
authors.lastname: Gagliardi
authors.forename: Angelo
authors.initials: A
authors.lastname: Bifone
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bardi
mesh_terms: D000588:Amines / Q000737:chemistry / Q000633:toxicity; D000818:Animals; D001812:Blood-Brain Barrier / Q000166:cytology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D050091:Dendrimers / Q000737:chemistry / Q000633:toxicity*; D042783:Endothelial Cells; D008055:Lipids / Q000737:chemistry / Q000633:toxicity; D051379:Mice; D017628:Microglia / Q000166:cytology*
chemical_list: D000588:Amines; D050091:Dendrimers; D008055:Lipids; C104700:PAMAM Starburst