Differential nanotoxicological and neuroinflammatory liabilities of non-viral vectors for RNA interference in the central nervous system.

Differential nanotoxicological and neuroinflammatory liabilities of non-viral vectors for RNA interference in the central nervous system. Biomaterials. 2013 Oct 16; Authors: Godinho BM, McCarthy DJ, Torres-Fuentes C, Beltrán CJ, McCarthy J, Quinlan A, Ogier JR, Darcy R, O'Driscoll CM, Cryan JF 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 in vitro 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 transfectio...
Source: Biomaterials - Category: Materials Science Authors: Tags: Biomaterials Source Type: research