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

摘要: Progression of RNA interference-based gene silencing technologies for the treatment disorders central nervous system (CNS) depends on availability efficient non-toxic nanocarriers. Despite advances in field nanotechnology undesired and non-specific interactions with different brain-cell types occur are poorly investigated. To this end, we studied cytotoxic neuroinflammatory effects widely-used transfection reagents modified amphiphilic β-cyclodextrins (CDs). All non-viral vectors formed positively charged nanoparticles distinctive physicochemical properties. Differential significant were observed among commercially available cationic vectors, whereas CDs induced limited disruptions cellular membrane integrity mitochondrial dehydrogenase activity. Interestingly, murine derived BV2 microglia cells a rat striatal vitro model Huntington's disease (ST14A-HTT120Q) more susceptible to toxicity than human U87 astroglioma cells. presented increases cytokine, toll-like receptor 2 cyclooxygenase-2 expression after selected commercial but not CD.siRNA nanoparticles. Non-viral siRNA formulated G6 polyamidoamine (PAMAM) also significantly increased cytokine brain following injections into mouse striatum. Together our data identify as nanosystems that enable delivery low levels cytotoxicity immunological activation.