The effect of dexamethasone/cell-penetrating peptide nanoparticles on gene delivery for inner ear therapy

Ji Young Yoon,1 Keum-Jin Yang,2 Shi-Nae Park,3 Dong-Kee Kim,3 Jong-Duk Kim1 1Department of Chemical and Biomolecular Engineering, BK 21 Plus Program, Korea Advanced Institute of Science and Technology, Guseong-Dong, Yuseong-Gu, Daejeon, 2Clinical Research Institute, St Mary’s Hospital, Da...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Yoon JY, Yang KJ, Park SN, Kim DK, Kim JD
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	cell penetrating peptide nanoparticle dexamethasone gene delivery brain-derived neurotrophic factor Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/2a57bd86e6d5457db0abf86c26648d0f
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:2a57bd86e6d5457db0abf86c26648d0f
record_format	dspace
spelling	oai:doaj.org-article:2a57bd86e6d5457db0abf86c26648d0f2021-12-02T01:14:33ZThe effect of dexamethasone/cell-penetrating peptide nanoparticles on gene delivery for inner ear therapy1178-2013https://doaj.org/article/2a57bd86e6d5457db0abf86c26648d0f2016-11-01T00:00:00Zhttps://www.dovepress.com/the-effect-of-dexamethasonecell-penetrating-peptide-nanoparticles-on-g-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Ji Young Yoon,1 Keum-Jin Yang,2 Shi-Nae Park,3 Dong-Kee Kim,3 Jong-Duk Kim1 1Department of Chemical and Biomolecular Engineering, BK 21 Plus Program, Korea Advanced Institute of Science and Technology, Guseong-Dong, Yuseong-Gu, Daejeon, 2Clinical Research Institute, St Mary’s Hospital, Daejeon, 3Department of Otolaryngology – Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea Abstract: Dexamethasone (Dex)-loaded PHEA-g-C18-Arg8 (PCA) nanoparticles (PCA/Dex) were developed for the delivery of genes to determine the synergistic effect of Dex on gene expression. The cationic PCA nanoparticles were self-assembled to create cationic micelles containing an octadecylamine (C18) core with Dex and an arginine 8 (Arg8) peptide shell for electrostatic complexation with nucleic acids (connexin 26 [Cx26] siRNA, green fluorescent protein [GFP] DNA or brain-derived neurotrophic factor [BDNF] pDNA). The PCA/Dex nanoparticles conjugated with Arg8, a cell-penetrating peptide that enhances permeability through a round window membrane in the inner ear for gene delivery, exhibited high uptake efficiency in HEI-OC1 cells. This potential carrier co-delivering Dex and the gene into inner ear cells has a diameter of 120–140 nm and a zeta potential of 20–25 mV. Different types of genes were complexed with the Dex-loaded PCA nanoparticle (PCA/Dex/gene) for gene expression to induce additional anti-inflammatory effects. PCA/Dex showed mildly increased expression of GFP and lower mRNA expression of inflammatory cytokines (IL1b, IL12, and INFr) than did Dex-free PCA nanoparticles and Lipofectamine® reagent in HEI-OC1 cells. In addition, after loading Cx26 siRNA onto the surface of PCA/Dex, Cx26 gene expression was downregulated according to real-time polymerase chain reaction for 24 h, compared with that using Lipofectamine reagent. After loading BDNF DNA into PCA/Dex, increased expression of BDNF was observed for 30 h, and its signaling pathway resulted in an increase in phosphorylation of Akt, observed by Western blotting. Thus, Dex within PCA/Dex/gene nanoparticles created an anti-inflammatory effect and enhanced gene expression. Keywords: cell-penetrating peptide, nanoparticle, dexamethasone, gene delivery, brain-derived neurotrophic factorYoon JYYang KJPark SNKim DKKim JDDove Medical Pressarticlecell penetrating peptidenanoparticledexamethasonegene deliverybrain-derived neurotrophic factorMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 11, Pp 6123-6134 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	cell penetrating peptide nanoparticle dexamethasone gene delivery brain-derived neurotrophic factor Medicine (General) R5-920
spellingShingle	cell penetrating peptide nanoparticle dexamethasone gene delivery brain-derived neurotrophic factor Medicine (General) R5-920 Yoon JY Yang KJ Park SN Kim DK Kim JD The effect of dexamethasone/cell-penetrating peptide nanoparticles on gene delivery for inner ear therapy
description	Ji Young Yoon,1 Keum-Jin Yang,2 Shi-Nae Park,3 Dong-Kee Kim,3 Jong-Duk Kim1 1Department of Chemical and Biomolecular Engineering, BK 21 Plus Program, Korea Advanced Institute of Science and Technology, Guseong-Dong, Yuseong-Gu, Daejeon, 2Clinical Research Institute, St Mary’s Hospital, Daejeon, 3Department of Otolaryngology – Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea Abstract: Dexamethasone (Dex)-loaded PHEA-g-C18-Arg8 (PCA) nanoparticles (PCA/Dex) were developed for the delivery of genes to determine the synergistic effect of Dex on gene expression. The cationic PCA nanoparticles were self-assembled to create cationic micelles containing an octadecylamine (C18) core with Dex and an arginine 8 (Arg8) peptide shell for electrostatic complexation with nucleic acids (connexin 26 [Cx26] siRNA, green fluorescent protein [GFP] DNA or brain-derived neurotrophic factor [BDNF] pDNA). The PCA/Dex nanoparticles conjugated with Arg8, a cell-penetrating peptide that enhances permeability through a round window membrane in the inner ear for gene delivery, exhibited high uptake efficiency in HEI-OC1 cells. This potential carrier co-delivering Dex and the gene into inner ear cells has a diameter of 120–140 nm and a zeta potential of 20–25 mV. Different types of genes were complexed with the Dex-loaded PCA nanoparticle (PCA/Dex/gene) for gene expression to induce additional anti-inflammatory effects. PCA/Dex showed mildly increased expression of GFP and lower mRNA expression of inflammatory cytokines (IL1b, IL12, and INFr) than did Dex-free PCA nanoparticles and Lipofectamine® reagent in HEI-OC1 cells. In addition, after loading Cx26 siRNA onto the surface of PCA/Dex, Cx26 gene expression was downregulated according to real-time polymerase chain reaction for 24 h, compared with that using Lipofectamine reagent. After loading BDNF DNA into PCA/Dex, increased expression of BDNF was observed for 30 h, and its signaling pathway resulted in an increase in phosphorylation of Akt, observed by Western blotting. Thus, Dex within PCA/Dex/gene nanoparticles created an anti-inflammatory effect and enhanced gene expression. Keywords: cell-penetrating peptide, nanoparticle, dexamethasone, gene delivery, brain-derived neurotrophic factor
format	article
author	Yoon JY Yang KJ Park SN Kim DK Kim JD
author_facet	Yoon JY Yang KJ Park SN Kim DK Kim JD
author_sort	Yoon JY
title	The effect of dexamethasone/cell-penetrating peptide nanoparticles on gene delivery for inner ear therapy
title_short	The effect of dexamethasone/cell-penetrating peptide nanoparticles on gene delivery for inner ear therapy
title_full	The effect of dexamethasone/cell-penetrating peptide nanoparticles on gene delivery for inner ear therapy
title_fullStr	The effect of dexamethasone/cell-penetrating peptide nanoparticles on gene delivery for inner ear therapy
title_full_unstemmed	The effect of dexamethasone/cell-penetrating peptide nanoparticles on gene delivery for inner ear therapy
title_sort	effect of dexamethasone/cell-penetrating peptide nanoparticles on gene delivery for inner ear therapy
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/2a57bd86e6d5457db0abf86c26648d0f
work_keys_str_mv	AT yoonjy theeffectofdexamethasonecellpenetratingpeptidenanoparticlesongenedeliveryforinnereartherapy AT yangkj theeffectofdexamethasonecellpenetratingpeptidenanoparticlesongenedeliveryforinnereartherapy AT parksn theeffectofdexamethasonecellpenetratingpeptidenanoparticlesongenedeliveryforinnereartherapy AT kimdk theeffectofdexamethasonecellpenetratingpeptidenanoparticlesongenedeliveryforinnereartherapy AT kimjd theeffectofdexamethasonecellpenetratingpeptidenanoparticlesongenedeliveryforinnereartherapy AT yoonjy effectofdexamethasonecellpenetratingpeptidenanoparticlesongenedeliveryforinnereartherapy AT yangkj effectofdexamethasonecellpenetratingpeptidenanoparticlesongenedeliveryforinnereartherapy AT parksn effectofdexamethasonecellpenetratingpeptidenanoparticlesongenedeliveryforinnereartherapy AT kimdk effectofdexamethasonecellpenetratingpeptidenanoparticlesongenedeliveryforinnereartherapy AT kimjd effectofdexamethasonecellpenetratingpeptidenanoparticlesongenedeliveryforinnereartherapy
_version_	1718403188625768448

The effect of dexamethasone/cell-penetrating peptide nanoparticles on gene delivery for inner ear therapy

Ejemplares similares