Back to Search
Start Over
Gold nanorods/siRNA complex administration for knockdown of PARP-1: a potential treatment for perinatal asphyxia
- Source :
- International Journal of Nanomedicine, Vol Volume 13, Pp 6839-6854 (2018)
- Publication Year :
- 2018
- Publisher :
- Dove Medical Press, 2018.
-
Abstract
- Valentina Vio,1,2 Ana L Riveros,1 Andrea Tapia-Bustos,2 Carolyne Lespay-Rebolledo,2 Ronald Perez-Lobos,2 Luis Muñoz,3 Paola Pismante,3 Paola Morales,2,4 Eyleen Araya,5 Natalia Hassan,1,6 Mario Herrera-Marschitz,2 Marcelo J Kogan1,7 1Department of Pharmacological and Toxicology Chemistry, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile; 2Program of Molecular and Clinical Pharmacology, Medical Faculty, Universidad de Chile, Santiago, Chile; 3Chemical Meteorology Section, Comisión Chilena de Energía Nuclear, Santiago, Chile; 4Department of Neuroscience, Faculty of Medicine, Universidad de Chile, Santiago, Chile; 5Departamento de Ciencias Quimicas, Facultad de Ciencias Exactas, Universidad Andres Bello, Santiago, Chile; 6Programa Institucional de Fomento a la Investigación, Desarrollo e Innovación, Universidad Tecnológica Metropolitana, Santiago, Chile; 7Advanced Center for Chronic Diseases (ACCDiS), Santiago, Chile 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. Keywords: neonatal hypoxia, siRNA delivery, PARP-1 knockdown, gold nanorods, in vivo administration, PC12, rats
Details
- Language :
- English
- ISSN :
- 11782013
- Volume :
- ume 13
- Database :
- Directory of Open Access Journals
- Journal :
- International Journal of Nanomedicine
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.0134da4d510452eaf66407526d5d96d
- Document Type :
- article