1. Departamento de Histología, Embriología, Biología Celular y Genética, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina;2. Laboratorio de Neuropatología Molecular, Instituto de Biología Celular y Neurociencia “Prof. E. De Robertis” IBCN UBA‐CONICET, Buenos Aires, Argentina;3. Programa de Nanomedicinas, Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, Bernal, Argentina
Abstract:
Secondary neuronal death is a serious stroke complication. This process is facilitated by the conversion of glial cells to the reactive pro‐inflammatory phenotype that induces neurodegeneration. Therefore, regulation of glial activation is a compelling strategy to reduce brain damage after stroke. However, drugs have difficulties to access the CNS , and to specifically target glial cells. In the present work, we explored the use core‐shell polyamidoamine tecto‐dendrimer (G5G2.5 PAMAM ) and studied its ability to target distinct populations of stroke‐activated glial cells. We found that G5G2.5 tecto‐dendrimer is actively engulfed by primary glial cells in a time‐ and dose‐dependent manner showing high cellular selectivity and lysosomal localization. In addition, oxygen‐glucose deprivation or lipopolysaccharides exposure in vitro and brain ischemia in vivo increase glial G5G2.5 uptake; not being incorporated by neurons or other cell types. We conclude that G5G2.5 tecto‐dendrimer is a highly suitable carrier for targeted drug delivery to reactive glial cells in vitro and in vivo after brain ischemia.
