Folic acid-functionalized polyethylenimine superparamagnetic iron oxide nanoparticles as theranostic agents for magnetic resonance imaging and PD-L1 siRNA delivery for gastric cancer

Xin Luo,1,* Xia Peng,1,* Jingying Hou,2 Shuyun Wu,3 Jun Shen,4 Lingyun Wang1 1Department of Gastroenterology, 2Department of Emergency Medicine, Sun Yat-sen Memorial Hospital, 3Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, 4Department of Radiology, Sun Yat-sen Memorial Hospi...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Luo X, Peng X, Hou J, Wu S, Shen J, Wang L
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	magnetic resonance imaging theranostics RNA interfering PEI cellular internalization Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/82a289864bc04342acccb24a1894bec1
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:82a289864bc04342acccb24a1894bec1
record_format	dspace
spelling	oai:doaj.org-article:82a289864bc04342acccb24a1894bec12021-12-02T00:45:23ZFolic acid-functionalized polyethylenimine superparamagnetic iron oxide nanoparticles as theranostic agents for magnetic resonance imaging and PD-L1 siRNA delivery for gastric cancer1178-2013https://doaj.org/article/82a289864bc04342acccb24a1894bec12017-07-01T00:00:00Zhttps://www.dovepress.com/folic-acid-functionalized-polyethylenimine-superparamagnetic-iron-oxid-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Xin Luo,1,* Xia Peng,1,* Jingying Hou,2 Shuyun Wu,3 Jun Shen,4 Lingyun Wang1 1Department of Gastroenterology, 2Department of Emergency Medicine, Sun Yat-sen Memorial Hospital, 3Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, 4Department of Radiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China *These authors contributed equally to this work Abstract: Programmed death ligand-1 (PD-L1), which is highly expressed in gastric cancers, interacts with programmed death-1 (PD-1) on T cells and is involved in T-cell immune resistance. To increase the therapeutic safety and accuracy of PD-1/PD-L1 blockade, RNA interference through targeted gene delivery was performed in our study. We developed folic acid (FA)- and disulfide (SS)–polyethylene glycol (PEG)-conjugated polyethylenimine (PEI) complexed with superparamagnetic iron oxide Fe3O4 nanoparticles (SPIONs) as a siRNA-delivery system for PD-L1 knockdown. The characterization, binding ability, cytotoxicity, transfection efficiency, and cellular internalization of the polyplex were determined. At nitrogen:phosphate (N:P) ratios of 10 or above, the FA-PEG-SS-PEI-SPIONs bound to PD-L1 siRNA to form a polyplex with a diameter of approximately 120 nm. Cell-viability assays showed that the polyplex had minimal cytotoxicity at low N:P ratios. The FA-conjugated polyplex showed higher transfection efficiency and cellular internalization in the folate receptor-overexpressing gastric cancer cell line SGC-7901 than a non-FA-conjugated polyplex. Subsequently, we adopted the targeted FA-PEG-SS-PEI-SPION/siRNA polyplexes at an N:P ratio of 10 for function studies. Cellular magnetic resonance imaging (MRI) showed that the polyplex could also act as a T2-weighted contrast agent for cancer MRI. Furthermore, one of four PD-L1 siRNAs exhibited effective PD-L1 knockdown in PD-L1-overexpressing SGC-7901. To determine the effects of the functionalized polyplex on T-cell function, we established a coculture model of activated T cells and SGC-7901 cells and demonstrated changes in secreted cytokines. Our findings highlight the potential of this class of multifunctional theranostic nanoparticles for effective targeted PD-L1-knockdown therapy and MRI diagnosis in gastric cancers. Keywords: magnetic resonance imaging, theranostics, RNA interference, PEI, cellular internalizationLuo XPeng XHou JWu SShen JWang LDove Medical Pressarticlemagnetic resonance imagingtheranosticsRNA interferingPEIcellular internalizationMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 5331-5343 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	magnetic resonance imaging theranostics RNA interfering PEI cellular internalization Medicine (General) R5-920
spellingShingle	magnetic resonance imaging theranostics RNA interfering PEI cellular internalization Medicine (General) R5-920 Luo X Peng X Hou J Wu S Shen J Wang L Folic acid-functionalized polyethylenimine superparamagnetic iron oxide nanoparticles as theranostic agents for magnetic resonance imaging and PD-L1 siRNA delivery for gastric cancer
description	Xin Luo,1,* Xia Peng,1,* Jingying Hou,2 Shuyun Wu,3 Jun Shen,4 Lingyun Wang1 1Department of Gastroenterology, 2Department of Emergency Medicine, Sun Yat-sen Memorial Hospital, 3Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, 4Department of Radiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China *These authors contributed equally to this work Abstract: Programmed death ligand-1 (PD-L1), which is highly expressed in gastric cancers, interacts with programmed death-1 (PD-1) on T cells and is involved in T-cell immune resistance. To increase the therapeutic safety and accuracy of PD-1/PD-L1 blockade, RNA interference through targeted gene delivery was performed in our study. We developed folic acid (FA)- and disulfide (SS)–polyethylene glycol (PEG)-conjugated polyethylenimine (PEI) complexed with superparamagnetic iron oxide Fe3O4 nanoparticles (SPIONs) as a siRNA-delivery system for PD-L1 knockdown. The characterization, binding ability, cytotoxicity, transfection efficiency, and cellular internalization of the polyplex were determined. At nitrogen:phosphate (N:P) ratios of 10 or above, the FA-PEG-SS-PEI-SPIONs bound to PD-L1 siRNA to form a polyplex with a diameter of approximately 120 nm. Cell-viability assays showed that the polyplex had minimal cytotoxicity at low N:P ratios. The FA-conjugated polyplex showed higher transfection efficiency and cellular internalization in the folate receptor-overexpressing gastric cancer cell line SGC-7901 than a non-FA-conjugated polyplex. Subsequently, we adopted the targeted FA-PEG-SS-PEI-SPION/siRNA polyplexes at an N:P ratio of 10 for function studies. Cellular magnetic resonance imaging (MRI) showed that the polyplex could also act as a T2-weighted contrast agent for cancer MRI. Furthermore, one of four PD-L1 siRNAs exhibited effective PD-L1 knockdown in PD-L1-overexpressing SGC-7901. To determine the effects of the functionalized polyplex on T-cell function, we established a coculture model of activated T cells and SGC-7901 cells and demonstrated changes in secreted cytokines. Our findings highlight the potential of this class of multifunctional theranostic nanoparticles for effective targeted PD-L1-knockdown therapy and MRI diagnosis in gastric cancers. Keywords: magnetic resonance imaging, theranostics, RNA interference, PEI, cellular internalization
format	article
author	Luo X Peng X Hou J Wu S Shen J Wang L
author_facet	Luo X Peng X Hou J Wu S Shen J Wang L
author_sort	Luo X
title	Folic acid-functionalized polyethylenimine superparamagnetic iron oxide nanoparticles as theranostic agents for magnetic resonance imaging and PD-L1 siRNA delivery for gastric cancer
title_short	Folic acid-functionalized polyethylenimine superparamagnetic iron oxide nanoparticles as theranostic agents for magnetic resonance imaging and PD-L1 siRNA delivery for gastric cancer
title_full	Folic acid-functionalized polyethylenimine superparamagnetic iron oxide nanoparticles as theranostic agents for magnetic resonance imaging and PD-L1 siRNA delivery for gastric cancer
title_fullStr	Folic acid-functionalized polyethylenimine superparamagnetic iron oxide nanoparticles as theranostic agents for magnetic resonance imaging and PD-L1 siRNA delivery for gastric cancer
title_full_unstemmed	Folic acid-functionalized polyethylenimine superparamagnetic iron oxide nanoparticles as theranostic agents for magnetic resonance imaging and PD-L1 siRNA delivery for gastric cancer
title_sort	folic acid-functionalized polyethylenimine superparamagnetic iron oxide nanoparticles as theranostic agents for magnetic resonance imaging and pd-l1 sirna delivery for gastric cancer
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/82a289864bc04342acccb24a1894bec1
work_keys_str_mv	AT luox folicacidfunctionalizedpolyethyleniminesuperparamagneticironoxidenanoparticlesastheranosticagentsformagneticresonanceimagingandpdl1sirnadeliveryforgastriccancer AT pengx folicacidfunctionalizedpolyethyleniminesuperparamagneticironoxidenanoparticlesastheranosticagentsformagneticresonanceimagingandpdl1sirnadeliveryforgastriccancer AT houj folicacidfunctionalizedpolyethyleniminesuperparamagneticironoxidenanoparticlesastheranosticagentsformagneticresonanceimagingandpdl1sirnadeliveryforgastriccancer AT wus folicacidfunctionalizedpolyethyleniminesuperparamagneticironoxidenanoparticlesastheranosticagentsformagneticresonanceimagingandpdl1sirnadeliveryforgastriccancer AT shenj folicacidfunctionalizedpolyethyleniminesuperparamagneticironoxidenanoparticlesastheranosticagentsformagneticresonanceimagingandpdl1sirnadeliveryforgastriccancer AT wangl folicacidfunctionalizedpolyethyleniminesuperparamagneticironoxidenanoparticlesastheranosticagentsformagneticresonanceimagingandpdl1sirnadeliveryforgastriccancer
_version_	1718403509186985984

Folic acid-functionalized polyethylenimine superparamagnetic iron oxide nanoparticles as theranostic agents for magnetic resonance imaging and PD-L1 siRNA delivery for gastric cancer

Ejemplares similares