Gold nanorods/siRNA complex administration for knockdown of PARP-1: A potential treatment for perinatal asphyxia
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Archivos
Fecha
2018
Profesor/a Guía
Facultad/escuela
Idioma
en
Título de la revista
ISSN de la revista
Título del volumen
Editor
Dove Medical Press Ltd.
Nombre de Curso
Licencia CC
CC BY-NC 4.0
Licencia CC
Resumen
Background: Perinatal asphyxia interferes with neonatal development, resulting in long-term deficits associated with systemic and neurological diseases. Despite the important role of poly (ADP-ribose) polymerase 1 (PARP-1) in the regulation of gene expression and DNA repair, overactivation of PARP-1 in asphyxia-exposed animals worsens the ATP-dependent energetic crisis. Inhibition of PARP-1 offers a therapeutic strategy for diminishing the effects of perinatal asphyxia. Methods: We designed a nanosystem that incorporates a specific siRNA for PARP-1 knockdown. The siRNA was complexed with gold nanorods (AuNR) conjugated to the peptide CLPFFD for brain targeting. Results: The siRNA was efficiently delivered into PC12 cells, resulting in gene silencing. The complex was administered intraperitoneally in vivo to asphyxia-exposed rat pups, and the ability of the AuNR-CLPFFD/siRNA complex to reach the brain was demonstrated. Conclusion: The combination of a nanosystem for delivery and a specific siRNA for gene silencing resulted in effective inhibition of PARP-1 in vivo. © 2018 Vio et al.
Notas
Indexación Scopus
Palabras clave
ADP-ribosylation, Poly ADP-ribose Glycohydrolase, DNA Damage, Gold nanorods, In vivo administration, Neonatal hypoxia, siRNA delivery
Citación
International Journal of Nanomedicine Volume 13, Pages 6839 - 6854 2018
DOI
10.2147/IJN.S175076