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


ABSTRACT:

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.

SUBMITTER: Vio V 

PROVIDER: S-EPMC6207385 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

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

Vio Valentina V   Riveros Ana L AL   Tapia-Bustos Andrea A   Lespay-Rebolledo Carolyne C   Perez-Lobos Ronald R   Muñoz Luis L   Pismante Paola P   Morales Paola P   Araya Eyleen E   Hassan Natalia N   Herrera-Marschitz Mario M   Kogan Marcelo J MJ  

International journal of nanomedicine 20181025


<h4>Background</h4>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.<h4>Methods</h4>We  ...[more]

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