title: Ionizing radiation-engineered nanogels as insulin nanocarriers for the development of a new strategy for the treatment of Alzheimer's disease.
abstract: A growing body of evidence shows the protective role of insulin in Alzheimer's disease (AD). A nanogel system (NG) to deliver insulin to the brain, as a tool for the development of a new therapy for Alzheimer's Disease (AD), is designed and synthetized. A carboxyl-functionalized poly(N-vinyl pyrrolidone) nanogel system produced by ionizing radiation is chosen as substrate for the covalent attachment of insulin or fluorescent molecules relevant for its characterization. Biocompatibility and hemocompatibility of the naked carrier is demonstrated. The insulin conjugated to the NG (NG-In) is protected by protease degradation and able to bind to insulin receptor (IR), as demonstrated by immunofluorescence measurements showing colocalization of NG-In(FITC) with IR. Moreover, after binding to the receptor, NG-In is able to trigger insulin signaling via AKT activation. Neuroprotection of NG-In against dysfunction induced by amyloid β (Aβ), a peptide mainly involved in AD, is verified. Finally, the potential of NG-In to be efficiently transported across the Blood Brain Barrier (BBB) is demonstrated. All together these results indicate that the synthesized NG-In is a suitable vehicle system for insulin deliver in biomedicine and a very promising tool to develop new therapies for neurodegenerative diseases.
authors.affiliation: Istituto di Biomedicina e Immunologia Molecolare "A. Monroy" (IBIM), Consiglio Nazionale delle Ricerche, Via U. La Malfa, 153, 90146 Palermo (PA), Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Picone
authors.affiliation: Dipartimento di Ingegneria Chimica, Gestionale, Informatica, Meccanica, Università di Palermo, Viale delle Scienze, Building 6, 90128 Palermo (PA), Italy.
authors.forename: Lorena Anna
authors.initials: LA
authors.lastname: Ditta
authors.affiliation: Dipartimento di Ingegneria Chimica, Gestionale, Informatica, Meccanica, Università di Palermo, Viale delle Scienze, Building 6, 90128 Palermo (PA), Italy.
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Sabatino
authors.affiliation: Dipartimento di Fisica e Chimica, Università di Palermo, Viale delle Scienze, Building 18, 90128 Palermo (PA), Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Militello
authors.affiliation: Istituto di BioFisica (IBF), Consiglio Nazionale delle Ricerche, Via U. La Malfa, 153, 90146 Palermo (PA), Italy.
authors.forename: Pier Luigi
authors.initials: PL
authors.lastname: San Biagio
authors.affiliation: Istituto di Biomedicina e Immunologia Molecolare "A. Monroy" (IBIM), Consiglio Nazionale delle Ricerche, Via U. La Malfa, 153, 90146 Palermo (PA), Italy.
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Di Giacinto
authors.affiliation: Istituto di Biomedicina e Immunologia Molecolare "A. Monroy" (IBIM), Consiglio Nazionale delle Ricerche, Via U. La Malfa, 153, 90146 Palermo (PA), Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Cristaldi
authors.affiliation: Istituto di Biomedicina e Immunologia Molecolare "A. Monroy" (IBIM), Consiglio Nazionale delle Ricerche, Via U. La Malfa, 153, 90146 Palermo (PA), Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Nuzzo
authors.affiliation: Dipartimento di Ingegneria Chimica, Gestionale, Informatica, Meccanica, Università di Palermo, Viale delle Scienze, Building 6, 90128 Palermo (PA), Italy; School of Chemical Science and Engineering, Department of Fiber and Polymer Technology, Royal Institute of Technology (KTH), SE-100 44, Stockholm, Sweden. Electronic address: clelia.dispenza@unipa.it.
authors.forename: Clelia
authors.initials: C
authors.lastname: Dispenza
authors.affiliation: Istituto di BioFisica (IBF), Consiglio Nazionale delle Ricerche, Via U. La Malfa, 153, 90146 Palermo (PA), Italy. Electronic address: daniela.giacomazza@cnr.it.
authors.forename: Daniela
authors.initials: D
authors.lastname: Giacomazza
authors.affiliation: Istituto di Biomedicina e Immunologia Molecolare "A. Monroy" (IBIM), Consiglio Nazionale delle Ricerche, Via U. La Malfa, 153, 90146 Palermo (PA), Italy. Electronic address: marta.dicarlo@ibim.cnr.it.
authors.forename: Marta
authors.initials: M
authors.lastname: Di Carlo
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D006801:Humans; D007328:Insulin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D008810:Mice, Inbred C57BL; D049329:Nanostructures / Q000737:chemistry / Q000528:radiation effects; D036103:Nanotechnology / Q000379:methods; D011205:Povidone / Q000737:chemistry*; D011839:Radiation, Ionizing; D011972:Receptor, Insulin / Q000378:metabolism
chemical_list: D004337:Drug Carriers; D007328:Insulin; D011972:Receptor, Insulin; D011205:Povidone
keywords: Alzheimer's disease; Insulin nanocarriers; Ionizing radiation processing; Nanogels; Targeted drug delivery