Autor según el artículo: Godinho, BMDC; McCarthy, DJ; Torres-Fuentes, C; Beltrán, CJ; McCarthy, J; Quinlan, A; Ogier, JR; Darcy, R; O'Driscoll, CM; Cryan, JF
Departamento: Bioquímica i Biotecnologia
Autor/es de la URV: Torres Fuentes, Cristina
Palabras clave: Toll-like receptors Stereotaxic Sirna High content analysis Cytokines Cyclodextrins toll-like receptors stereotaxic high content analysis cytokines cyclodextrins
Resumen: 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.
Áreas temáticas: 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
Acceso a la licencia de uso: https://creativecommons.org/licenses/by/3.0/es/
ISSN: 01429612
Direcció de correo del autor: cristina.torres@urv.cat
Identificador del autor: 0000-0002-2917-6910
Fecha de alta del registro: 2024-09-07
Versión del articulo depositado: info:eu-repo/semantics/acceptedVersion
Enlace a la fuente original: https://www.sciencedirect.com/science/article/abs/pii/S014296121301168X?via%3Dihub
URL Documento de licencia: https://repositori.urv.cat/ca/proteccio-de-dades/
Referencia al articulo segun fuente origial: Biomaterials. 35 (1): 489-499
Referencia de l'ítem segons les normes 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
DOI del artículo: 10.1016/j.biomaterials.2013.09.068
Entidad: Universitat Rovira i Virgili
Año de publicación de la revista: 2014
Tipo de publicación: Journal Publications