title: Investigation of Functionalized Poly(N,N-dimethylacrylamide)-block-polystyrene Nanoparticles As Novel Drug Delivery System to Overcome the Blood-Brain Barrier In Vitro.
abstract: In the search of new drug delivery carriers for the brain, self-assembled nanoparticles (NP) were prepared from poly(N,N-dimethylacrylamide)-block-polystyrene polymer. NP displayed biocompatibility on cultured endothelial cells, macrophages and differentiated SH-SY5Y neuronal-like cells. The surface-functionalization of NP with a modified fragment of human Apolipoprotein E (mApoE) enhanced the uptake of NP by cultured human brain capillary endothelial cells, as assessed by confocal microscopy, and their permeability through a Transwell Blood Brain Barrier model made with the same cells, as assessed by fluorescence. Finally, mApoE-NP embedding doxorubicin displayed an enhanced release of drug at low pH, suggesting the potential use of these NP for the treatment of brain tumors.
authors.affiliation: Department of Health Sciences, Nanomedicine Center NANOMIB, University of Milano-Bicocca, via Cadore 48, 20900, Monza, Italy. maria.gregori1@unimib.it.
authors.forename: Maria
authors.initials: M
authors.lastname: Gregori
authors.affiliation: Department of Materials Science, University of Milano-Bicocca, Via Roberto Cozzi 55, 20125, Milano, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Bertani
authors.affiliation: Department of Health Sciences, Nanomedicine Center NANOMIB, University of Milano-Bicocca, via Cadore 48, 20900, Monza, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Cazzaniga
authors.affiliation: Department of Health Sciences, Nanomedicine Center NANOMIB, University of Milano-Bicocca, via Cadore 48, 20900, Monza, Italy.
authors.forename: Antonina
authors.initials: A
authors.lastname: Orlando
authors.affiliation: Department of Materials Science, University of Milano-Bicocca, Via Roberto Cozzi 55, 20125, Milano, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Mauri
authors.affiliation: Department of Materials Science, University of Milano-Bicocca, Via Roberto Cozzi 55, 20125, Milano, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Bianchi
authors.affiliation: Department of Health Sciences, Nanomedicine Center NANOMIB, University of Milano-Bicocca, via Cadore 48, 20900, Monza, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Re
authors.affiliation: Department of Health Sciences, Nanomedicine Center NANOMIB, University of Milano-Bicocca, via Cadore 48, 20900, Monza, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Sesana
authors.affiliation: Department of Health Sciences, Nanomedicine Center NANOMIB, University of Milano-Bicocca, via Cadore 48, 20900, Monza, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Minniti
authors.affiliation: Department of Medical Biotechnology and Translational Medicine, University of Milano and Fondazione Filarete, Via Vanvitelli 32, 20129, Milano, Italy.
authors.forename: Maura
authors.initials: M
authors.lastname: Francolini
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, IRCCS Mario Negri Institute for Pharmacological Research, Via La Masa 19, 20156, Milano, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Cagnotto
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, IRCCS Mario Negri Institute for Pharmacological Research, Via La Masa 19, 20156, Milano, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Salmona
authors.affiliation: Department of Health Sciences, Nanomedicine Center NANOMIB, University of Milano-Bicocca, via Cadore 48, 20900, Monza, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Nardo
authors.affiliation: Department of Health Sciences, Nanomedicine Center NANOMIB, University of Milano-Bicocca, via Cadore 48, 20900, Monza, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Salerno
authors.affiliation: Department of Health Sciences, Nanomedicine Center NANOMIB, University of Milano-Bicocca, via Cadore 48, 20900, Monza, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Mantegazza
authors.affiliation: Department of Health Sciences, Nanomedicine Center NANOMIB, University of Milano-Bicocca, via Cadore 48, 20900, Monza, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Masserini
authors.affiliation: Department of Materials Science, University of Milano-Bicocca, Via Roberto Cozzi 55, 20125, Milano, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Simonutti
mesh_terms: D000178:Acrylamides / Q000737:chemistry*; D001057:Apolipoproteins E / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002460:Cell Line; D004317:Doxorubicin / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D011137:Polystyrenes / Q000737:chemistry*
chemical_list: D000178:Acrylamides; D001057:Apolipoproteins E; D004337:Drug Carriers; D011137:Polystyrenes; C429790:poly(N,N-dimethylacrylamide); D004317:Doxorubicin
keywords: blood-brain barrier; controlled drug release; copolymers; drug delivery; nanoparticles