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Gold nanorods/siRNA complex administration for knockdown of PARP-1: a potential treatment for perinatal asphyxia

2018; Dove Medical Press; Volume: Volume 13; Linguagem: Inglês

10.2147/ijn.s175076

1178-2013

Valentina Vío, Ana Riveros, Andrea Tapia-Bustos, Carolyne Lespay‐Rebolledo, Ronald Pérez-Lobos, Luis Muñoz, Paola Pismante, Paola Morales, Eyleen Araya, Natalia Hassan, Mario Herrera‐Marschitz, Marcelo J. Kogan,

Nanopore and Nanochannel Transport Studies

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.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.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.The combination of a nanosystem for delivery and a specific siRNA for gene silencing resulted in effective inhibition of PARP-1 in vivo.