Gold nanorods/siRNA complex administration for knockdown of PARP-1: a potential treatment for perinatal asphyxia
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,...
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Dove Medical Press
2018
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oai:doaj.org-article:d0134da4d510452eaf66407526d5d96d2021-12-02T05:05:06ZGold nanorods/siRNA complex administration for knockdown of PARP-1: a potential treatment for perinatal asphyxia1178-2013https://doaj.org/article/d0134da4d510452eaf66407526d5d96d2018-10-01T00:00:00Zhttps://www.dovepress.com/gold-nanorodssirna-complex-administration-for-knockdown-of-parp-1-a-po-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Valentina 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, ratsVio VRiveros ALTapia-Bustos ALespay-Rebolledo CPerez-Lobos RMuñoz LPismante PMorales PAraya EHassan NHerrera-Marschitz MKogan MJDove Medical Pressarticleneonatal hypoxiasiRNA deliveryPARP-1 knockdowngold nanorodsin vivo administrationPC12ratsMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 6839-6854 (2018) |
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EN |
| topic |
neonatal hypoxia siRNA delivery PARP-1 knockdown gold nanorods in vivo administration PC12 rats Medicine (General) R5-920 |
| spellingShingle |
neonatal hypoxia siRNA delivery PARP-1 knockdown gold nanorods in vivo administration PC12 rats Medicine (General) R5-920 Vio V Riveros AL Tapia-Bustos A Lespay-Rebolledo C Perez-Lobos R Muñoz L Pismante P Morales P Araya E Hassan N Herrera-Marschitz M Kogan MJ Gold nanorods/siRNA complex administration for knockdown of PARP-1: a potential treatment for perinatal asphyxia |
| description |
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 |
| format |
article |
| author |
Vio V Riveros AL Tapia-Bustos A Lespay-Rebolledo C Perez-Lobos R Muñoz L Pismante P Morales P Araya E Hassan N Herrera-Marschitz M Kogan MJ |
| author_facet |
Vio V Riveros AL Tapia-Bustos A Lespay-Rebolledo C Perez-Lobos R Muñoz L Pismante P Morales P Araya E Hassan N Herrera-Marschitz M Kogan MJ |
| author_sort |
Vio V |
| title |
Gold nanorods/siRNA complex administration for knockdown of PARP-1: a potential treatment for perinatal asphyxia |
| title_short |
Gold nanorods/siRNA complex administration for knockdown of PARP-1: a potential treatment for perinatal asphyxia |
| title_full |
Gold nanorods/siRNA complex administration for knockdown of PARP-1: a potential treatment for perinatal asphyxia |
| title_fullStr |
Gold nanorods/siRNA complex administration for knockdown of PARP-1: a potential treatment for perinatal asphyxia |
| title_full_unstemmed |
Gold nanorods/siRNA complex administration for knockdown of PARP-1: a potential treatment for perinatal asphyxia |
| title_sort |
gold nanorods/sirna complex administration for knockdown of parp-1: a potential treatment for perinatal asphyxia |
| publisher |
Dove Medical Press |
| publishDate |
2018 |
| url |
https://doaj.org/article/d0134da4d510452eaf66407526d5d96d |
| work_keys_str_mv |
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