Author, as appears in the article.: Godinho, BMDC; McCarthy, DJ; Torres-Fuentes, C; Beltrán, CJ; McCarthy, J; Quinlan, A; Ogier, JR; Darcy, R; O'Driscoll, CM; Cryan, JF
Department: Bioquímica i Biotecnologia
URV's Author/s: Torres Fuentes, Cristina
Keywords: Toll-like receptors Stereotaxic Sirna High content analysis Cytokines Cyclodextrins toll-like receptors stereotaxic high content analysis cytokines cyclodextrins
Abstract: Progression of RNA interference-based gene silencing technologies for the treatment of disorders of the central nervous system (CNS) depends on the availability of efficient non-toxic nanocarriers. Despite advances in the field of nanotechnology undesired and non-specific interactions with different brain-cell types occur and are poorly investigated. To this end, we studied the cytotoxic and neuroinflammatory effects of widely-used transfection reagents and modified amphiphilic β-cyclodextrins (CDs). All non-viral vectors formed positively charged nanoparticles with distinctive physicochemical properties. Differential and significant cytotoxic effects were observed among commercially available cationic vectors, whereas CDs induced limited disruptions of cellular membrane integrity and mitochondrial dehydrogenase activity. Interestingly, murine derived BV2 microglia cells and a rat striatal invitro model of Huntington's disease (ST14A-HTT120Q) were more susceptible to toxicity than human U87 astroglioma cells. BV2 microglia presented significant increases in cytokine, toll-like receptor 2 and cyclooxygenase-2 gene expression after transfection with selected commercial vectors but not with CD.siRNA nanoparticles. Non-viral siRNA nanoparticles formulated with G6 polyamidoamine (PAMAM) also significantly increased cytokine gene expression in the brain following injections into the mouse striatum. Together our data identify modified CDs as nanosystems that enable siRNA delivery to the brain with low levels of cytotoxicity and immunological activation. © 2013 Elsevier Ltd.
Thematic Areas: Química Odontología Nanoscience and nanotechnology Medicina veterinaria Medicina ii Mechanics of materials Materials science, biomaterials Interdisciplinar General medicine Farmacia Engineering, biomedical Engenharias iv Engenharias ii Ciências biológicas ii Ciências biológicas i Ceramics and composites Biotecnología Biophysics Biomaterials Bioengineering Biodiversidade
licence for use: https://creativecommons.org/licenses/by/3.0/es/
ISSN: 01429612
Author's mail: cristina.torres@urv.cat
Author identifier: 0000-0002-2917-6910
Record's date: 2024-09-07
Papper version: info:eu-repo/semantics/acceptedVersion
Link to the original source: https://www.sciencedirect.com/science/article/abs/pii/S014296121301168X?via%3Dihub
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Papper original source: Biomaterials. 35 (1): 489-499
APA: Godinho, BMDC; McCarthy, DJ; Torres-Fuentes, C; Beltrán, CJ; McCarthy, J; Quinlan, A; Ogier, JR; Darcy, R; O'Driscoll, CM; Cryan, JF (2014). Differential nanotoxicological and neuroinflammatory liabilities of non-viral vectors for RNA interference in the central nervous system. Biomaterials, 35(1), 489-499. DOI: 10.1016/j.biomaterials.2013.09.068
Article's DOI: 10.1016/j.biomaterials.2013.09.068
Entity: Universitat Rovira i Virgili
Journal publication year: 2014
Publication Type: Journal Publications
Repositori URV