Codelivery of doxorubicin and JIP1 siRNA with novel EphA2-targeted PEGylated cationic nanoliposomes to overcome osteosarcoma multidrug resistance

Fateme Haghiralsadat,1–3 Ghasem Amoabediny,3–5 Samira Naderinezhad,4 Behrouz Zandieh-Doulabi,6 Tymour Forouzanfar,5 Marco N Helder5 1Department of Life Science Engineering, Faculty of New Sciences and Technologies, University of Tehran, Tehran, Iran; 2Department of Orthopaedic S...

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Autores principales:	Haghiralsadat F, Amoabediny G, Naderinezhad S, Zandieh-Doulabi B, Forouzanfar T, Helder MN
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	siRNA EphA2 targeting liposomal doxorubicin Osteosarcoma multi-drug resistance MAPK8IP1. Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/9c7daf8b126943e3949a1d0e70d1db36
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spelling	oai:doaj.org-article:9c7daf8b126943e3949a1d0e70d1db362021-12-02T01:09:50ZCodelivery of doxorubicin and JIP1 siRNA with novel EphA2-targeted PEGylated cationic nanoliposomes to overcome osteosarcoma multidrug resistance1178-2013https://doaj.org/article/9c7daf8b126943e3949a1d0e70d1db362018-07-01T00:00:00Zhttps://www.dovepress.com/codelivery-of-doxorubicin-and-jip1-sirna-with-novel-epha2-targeted-peg-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Fateme Haghiralsadat,1–3 Ghasem Amoabediny,3–5 Samira Naderinezhad,4 Behrouz Zandieh-Doulabi,6 Tymour Forouzanfar,5 Marco N Helder5 1Department of Life Science Engineering, Faculty of New Sciences and Technologies, University of Tehran, Tehran, Iran; 2Department of Orthopaedic Surgery, VU University Medical Center, MOVE Research Institute Amsterdam, Amsterdam, the Netherlands; 3Department of Nano Biotechnology, Research Center for New Technologies in Life Science Engineering, 4Department of Biotechnology and Pharmaceutical Engineering, School of Chemical Engineering, College of Engineering, University of Tehran, Tehran, Iran; 5Department of Oral and Maxillofacial Surgery, VU University Medical Center, MOVE Research Institute Amsterdam, 6Department of Oral Cell Biology and Functional Anatomy, Academic Center for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam and University of Amsterdam, MOVE Research Institute, Amsterdam, the Netherlands Purpose: Osteosarcoma (OS) mostly affects children and young adults, and has only a 20%–30% 5-year survival rate when metastasized. We aimed to create dual-targeted (extracellular against EphA2 and intracellular against JNK-interacting protein 1 [JIP1]), doxorubicin (DOX)-loaded liposomes to treat OS metastatic disease. Materials and methods: Cationic liposomes contained N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methyl-sulfate (DOTAP), cholesterol, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), and distearoyl-phosphatidylethanolamine–methyl-poly(ethylene glycol) (DSPE–mPEG) conjugate. EphA2 targeting was accomplished by conjugating YSA peptide to DSPE–mPEG. Vesicles were subsequently loaded with DOX and JIP1 siRNA. Results: Characteristics assessment showed that 1) size of the bilayered particles was 109 nm; 2) DOX loading efficiency was 87%; 3) siRNA could be successfully loaded at a liposome:siRNA ratio of >24:1; and 4) the zeta potential was 18.47 mV. Tumor-mimicking pH conditions exhibited 80% siRNA and 50.7% DOX sustained release from the particles. Stability studies ensured the protection of siRNA against degradation in serum. OS cell lines showed increased and more pericellular/nuclear localizations when using targeted vesicles. Nontargeted and targeted codelivery caused 70.5% and 78.6% cytotoxicity in OS cells, respectively (free DOX: 50%). Targeted codelivery resulted in 42% reduction in the siRNA target, JIP1 mRNA, and 46% decrease in JIP1 levels. Conclusion: Our dual-targeted, DOX-loaded liposomes enhance toxicity toward OS cells and may be effective for the treatment of metastatic OS. Keywords: MAP kinase 8 interacting protein 1, MAPK8IP1, functionalization, cationic liposome, intracellular targeting, extracellular targetingHaghiralsadat FAmoabediny GNaderinezhad SZandieh-Doulabi BForouzanfar THelder MNDove Medical PressarticlesiRNAEphA2 targetingliposomal doxorubicinOsteosarcomamulti-drug resistanceMAPK8IP1.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 3853-3866 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	siRNA EphA2 targeting liposomal doxorubicin Osteosarcoma multi-drug resistance MAPK8IP1. Medicine (General) R5-920
spellingShingle	siRNA EphA2 targeting liposomal doxorubicin Osteosarcoma multi-drug resistance MAPK8IP1. Medicine (General) R5-920 Haghiralsadat F Amoabediny G Naderinezhad S Zandieh-Doulabi B Forouzanfar T Helder MN Codelivery of doxorubicin and JIP1 siRNA with novel EphA2-targeted PEGylated cationic nanoliposomes to overcome osteosarcoma multidrug resistance
description	Fateme Haghiralsadat,1–3 Ghasem Amoabediny,3–5 Samira Naderinezhad,4 Behrouz Zandieh-Doulabi,6 Tymour Forouzanfar,5 Marco N Helder5 1Department of Life Science Engineering, Faculty of New Sciences and Technologies, University of Tehran, Tehran, Iran; 2Department of Orthopaedic Surgery, VU University Medical Center, MOVE Research Institute Amsterdam, Amsterdam, the Netherlands; 3Department of Nano Biotechnology, Research Center for New Technologies in Life Science Engineering, 4Department of Biotechnology and Pharmaceutical Engineering, School of Chemical Engineering, College of Engineering, University of Tehran, Tehran, Iran; 5Department of Oral and Maxillofacial Surgery, VU University Medical Center, MOVE Research Institute Amsterdam, 6Department of Oral Cell Biology and Functional Anatomy, Academic Center for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam and University of Amsterdam, MOVE Research Institute, Amsterdam, the Netherlands Purpose: Osteosarcoma (OS) mostly affects children and young adults, and has only a 20%–30% 5-year survival rate when metastasized. We aimed to create dual-targeted (extracellular against EphA2 and intracellular against JNK-interacting protein 1 [JIP1]), doxorubicin (DOX)-loaded liposomes to treat OS metastatic disease. Materials and methods: Cationic liposomes contained N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methyl-sulfate (DOTAP), cholesterol, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), and distearoyl-phosphatidylethanolamine–methyl-poly(ethylene glycol) (DSPE–mPEG) conjugate. EphA2 targeting was accomplished by conjugating YSA peptide to DSPE–mPEG. Vesicles were subsequently loaded with DOX and JIP1 siRNA. Results: Characteristics assessment showed that 1) size of the bilayered particles was 109 nm; 2) DOX loading efficiency was 87%; 3) siRNA could be successfully loaded at a liposome:siRNA ratio of >24:1; and 4) the zeta potential was 18.47 mV. Tumor-mimicking pH conditions exhibited 80% siRNA and 50.7% DOX sustained release from the particles. Stability studies ensured the protection of siRNA against degradation in serum. OS cell lines showed increased and more pericellular/nuclear localizations when using targeted vesicles. Nontargeted and targeted codelivery caused 70.5% and 78.6% cytotoxicity in OS cells, respectively (free DOX: 50%). Targeted codelivery resulted in 42% reduction in the siRNA target, JIP1 mRNA, and 46% decrease in JIP1 levels. Conclusion: Our dual-targeted, DOX-loaded liposomes enhance toxicity toward OS cells and may be effective for the treatment of metastatic OS. Keywords: MAP kinase 8 interacting protein 1, MAPK8IP1, functionalization, cationic liposome, intracellular targeting, extracellular targeting
format	article
author	Haghiralsadat F Amoabediny G Naderinezhad S Zandieh-Doulabi B Forouzanfar T Helder MN
author_facet	Haghiralsadat F Amoabediny G Naderinezhad S Zandieh-Doulabi B Forouzanfar T Helder MN
author_sort	Haghiralsadat F
title	Codelivery of doxorubicin and JIP1 siRNA with novel EphA2-targeted PEGylated cationic nanoliposomes to overcome osteosarcoma multidrug resistance
title_short	Codelivery of doxorubicin and JIP1 siRNA with novel EphA2-targeted PEGylated cationic nanoliposomes to overcome osteosarcoma multidrug resistance
title_full	Codelivery of doxorubicin and JIP1 siRNA with novel EphA2-targeted PEGylated cationic nanoliposomes to overcome osteosarcoma multidrug resistance
title_fullStr	Codelivery of doxorubicin and JIP1 siRNA with novel EphA2-targeted PEGylated cationic nanoliposomes to overcome osteosarcoma multidrug resistance
title_full_unstemmed	Codelivery of doxorubicin and JIP1 siRNA with novel EphA2-targeted PEGylated cationic nanoliposomes to overcome osteosarcoma multidrug resistance
title_sort	codelivery of doxorubicin and jip1 sirna with novel epha2-targeted pegylated cationic nanoliposomes to overcome osteosarcoma multidrug resistance
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/9c7daf8b126943e3949a1d0e70d1db36
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Codelivery of doxorubicin and JIP1 siRNA with novel EphA2-targeted PEGylated cationic nanoliposomes to overcome osteosarcoma multidrug resistance

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