CONICET | Buscador de Institutos y Recursos Humanos

Decreased long term disabilities after stroke are dependent on neuronal survival. Secondary neuronal death in the penumbra is facilitated by the conversion of glial cells to the proinflammatory phenotype that induces neurodegeneration. Therefore, regulation of glial activation is a compelling strategy to reduce brain damage after stroke. This regulation is challenging due to the difficulty of some drugs to access the central nervous system (CNS), and specifically target glial cells. Effective stoke therapy demands a carrier that can cross the blood-brain barrier, and target activated glial cells. Furthermore, activated glial cells (astrocytes and microglia) are a highly heterogenic population, with a broad, context dependent, spectrum of possible activation profiles. Given that different activation phenotypes can drive neuronal fate, it is important to include assorted activating stimuli. In the present work we set up to exploit the tailorable qualities of nanoparticles, and explored the use of a polyamidoamine core-shell tecto-dendrimer (G5G2.5 PAMAM) as a carrier for distinct populations of stroke activated glia. We found that G5G2.5 tecto-dendrimer is actively engulfed by glial cells in a time- and dose-dependent manner showing high cellular selectivity and lysosomal localization. In addition, in vitro oxygen-glucose deprivation (OGD) or lipopolysaccharide (LPS) exposure increased astroglial G5G2.5 uptake; but this was not observed in glial scar forming astrocytes. In vivo brain ischemia showed an increased incorporation of the tecto-dendrimer in the lesioned area, with specific preference for immune engaged cells. We conclude that G5G2.5 tecto-dendrimer is a highly suitable carrier for targeted drug delivery to glial cells after brain ischemia.Funding: Supported by grants of CONICET PIP 387 and 479 (to AJR), ANPCYT PICT2012-1424 and PICT2015-1451 (to AJR), UBACYT (to AJR)