Targeted delivery of let-7a microRNA encapsulated ephrin-A1 conjugated liposomal nanoparticles inhibit tumor growth in lung cancer

Hung-Yen Lee,1,2 Kamal A Mohammed,1,3 Fredric Kaye,4 Parvesh Sharma,5 Brij M Moudgil,5 William L Clapp,6 Najmunnisa Nasreen1,3 1Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine in the College of Medicine, 2Biomaterials Center, Department of Materials Sciences and Engin...

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Autores principales:	Lee HY, Mohammed KA, Kaye F, Sharma P, Moudgil BM, Clapp WL, Nasreen N
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/3b823284bc2a49209ed6cb26cb79d7ec
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spelling	oai:doaj.org-article:3b823284bc2a49209ed6cb26cb79d7ec2021-12-02T02:10:26ZTargeted delivery of let-7a microRNA encapsulated ephrin-A1 conjugated liposomal nanoparticles inhibit tumor growth in lung cancer1176-91141178-2013https://doaj.org/article/3b823284bc2a49209ed6cb26cb79d7ec2013-11-01T00:00:00Zhttp://www.dovepress.com/targeted-delivery-of-let-7a-microrna-encapsulated-ephrin-a1-conjugated-a15035https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Hung-Yen Lee,1,2 Kamal A Mohammed,1,3 Fredric Kaye,4 Parvesh Sharma,5 Brij M Moudgil,5 William L Clapp,6 Najmunnisa Nasreen1,3 1Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine in the College of Medicine, 2Biomaterials Center, Department of Materials Sciences and Engineering, 3North Florida/South Georgia Veterans Health System, Malcom Randall VA Medical Center, 4Division of Hematology and Oncology, Department of Medicine in the College of Medicine, 5Particle Engineering Research Center and Department of Materials Science and Engineering, 6Renal Pathology, Surgical Pathology, University of Florida, Gainesville, FL, USA Abstract: MicroRNAs (miRs) are small noncoding RNA sequences that negatively regulate the expression of target genes by posttranscriptional repression. miRs are dysregulated in various diseases, including cancer. let-7a miR, an antioncogenic miR, is downregulated in lung cancers. Our earlier studies demonstrated that let-7a miR inhibits tumor growth in malignant pleural mesothelioma (MPM) and could be a potential therapeutic against lung cancer. EphA2 (ephrin type-A receptor 2) tyrosine kinase is overexpressed in most cancer cells, including MPM and non-small-cell lung cancer (NSCLC) cells. Ephrin-A1, a specific ligand of the EphA2 receptor, inhibits cell proliferation and migration. In this study, to enhance the delivery of miR, the miRs were encapsulated in the DOTAP (N-[1-(2.3-dioleoyloxy)propyl]-N,N,N-trimethyl ammonium)/Cholesterol/DSPE (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[cyanur(polyethylene glycol)-2000])-PEG (polyethylene glycol)-cyanur liposomal nanoparticles (LNP) and ephrin-A1 was conjugated on the surface of LNP to target receptor EphA2 on lung cancer cells. The LNP with an average diameter of 100 nm showed high stability, low cytotoxicity, and high loading efficiency of precursor let-7a miR and ephrin-A1. The ephrin-A1 conjugated LNP (ephrin-A1–LNP) and let-7a miR encapsulated LNP (miR–LNP) showed improved transfection efficiency against MPM and NSCLC. The effectiveness of targeted delivery of let-7a miR encapsulated ephrin-A1 conjugated LNP (miR–ephrin-A1–LNP) was determined on MPM and NSCLC tumor growth in vitro. miR–ephrin-A1–LNP significantly increased the delivery of let-7a miR in lung cancer cells when compared with free let-7a miR. In addition, the expression of target gene Ras was significantly repressed following miR–ephrin-A1–LNP treatment. Furthermore, the miR–ephrin-A1–LNP complex significantly inhibited MPM and NSCLC proliferation, migration, and tumor growth. Our results demonstrate that the engineered miR–ephrin-A1–LNP complex is an effective carrier for the targeted delivery of small RNA molecules to lung cancer cells. This could be a potential therapeutic approach against tumors overexpressing the EphA2 receptor. Keywords: liposomal nanoparticles, EphA2 receptor, microRNA, ephrin-A1, malignant pleural mesothelioma, non-small-cell lung cancerLee HYMohammed KAKaye FSharma PMoudgil BMClapp WLNasreen NDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss Issue 1, Pp 4481-4494 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Lee HY Mohammed KA Kaye F Sharma P Moudgil BM Clapp WL Nasreen N Targeted delivery of let-7a microRNA encapsulated ephrin-A1 conjugated liposomal nanoparticles inhibit tumor growth in lung cancer
description	Hung-Yen Lee,1,2 Kamal A Mohammed,1,3 Fredric Kaye,4 Parvesh Sharma,5 Brij M Moudgil,5 William L Clapp,6 Najmunnisa Nasreen1,3 1Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine in the College of Medicine, 2Biomaterials Center, Department of Materials Sciences and Engineering, 3North Florida/South Georgia Veterans Health System, Malcom Randall VA Medical Center, 4Division of Hematology and Oncology, Department of Medicine in the College of Medicine, 5Particle Engineering Research Center and Department of Materials Science and Engineering, 6Renal Pathology, Surgical Pathology, University of Florida, Gainesville, FL, USA Abstract: MicroRNAs (miRs) are small noncoding RNA sequences that negatively regulate the expression of target genes by posttranscriptional repression. miRs are dysregulated in various diseases, including cancer. let-7a miR, an antioncogenic miR, is downregulated in lung cancers. Our earlier studies demonstrated that let-7a miR inhibits tumor growth in malignant pleural mesothelioma (MPM) and could be a potential therapeutic against lung cancer. EphA2 (ephrin type-A receptor 2) tyrosine kinase is overexpressed in most cancer cells, including MPM and non-small-cell lung cancer (NSCLC) cells. Ephrin-A1, a specific ligand of the EphA2 receptor, inhibits cell proliferation and migration. In this study, to enhance the delivery of miR, the miRs were encapsulated in the DOTAP (N-[1-(2.3-dioleoyloxy)propyl]-N,N,N-trimethyl ammonium)/Cholesterol/DSPE (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[cyanur(polyethylene glycol)-2000])-PEG (polyethylene glycol)-cyanur liposomal nanoparticles (LNP) and ephrin-A1 was conjugated on the surface of LNP to target receptor EphA2 on lung cancer cells. The LNP with an average diameter of 100 nm showed high stability, low cytotoxicity, and high loading efficiency of precursor let-7a miR and ephrin-A1. The ephrin-A1 conjugated LNP (ephrin-A1–LNP) and let-7a miR encapsulated LNP (miR–LNP) showed improved transfection efficiency against MPM and NSCLC. The effectiveness of targeted delivery of let-7a miR encapsulated ephrin-A1 conjugated LNP (miR–ephrin-A1–LNP) was determined on MPM and NSCLC tumor growth in vitro. miR–ephrin-A1–LNP significantly increased the delivery of let-7a miR in lung cancer cells when compared with free let-7a miR. In addition, the expression of target gene Ras was significantly repressed following miR–ephrin-A1–LNP treatment. Furthermore, the miR–ephrin-A1–LNP complex significantly inhibited MPM and NSCLC proliferation, migration, and tumor growth. Our results demonstrate that the engineered miR–ephrin-A1–LNP complex is an effective carrier for the targeted delivery of small RNA molecules to lung cancer cells. This could be a potential therapeutic approach against tumors overexpressing the EphA2 receptor. Keywords: liposomal nanoparticles, EphA2 receptor, microRNA, ephrin-A1, malignant pleural mesothelioma, non-small-cell lung cancer
format	article
author	Lee HY Mohammed KA Kaye F Sharma P Moudgil BM Clapp WL Nasreen N
author_facet	Lee HY Mohammed KA Kaye F Sharma P Moudgil BM Clapp WL Nasreen N
author_sort	Lee HY
title	Targeted delivery of let-7a microRNA encapsulated ephrin-A1 conjugated liposomal nanoparticles inhibit tumor growth in lung cancer
title_short	Targeted delivery of let-7a microRNA encapsulated ephrin-A1 conjugated liposomal nanoparticles inhibit tumor growth in lung cancer
title_full	Targeted delivery of let-7a microRNA encapsulated ephrin-A1 conjugated liposomal nanoparticles inhibit tumor growth in lung cancer
title_fullStr	Targeted delivery of let-7a microRNA encapsulated ephrin-A1 conjugated liposomal nanoparticles inhibit tumor growth in lung cancer
title_full_unstemmed	Targeted delivery of let-7a microRNA encapsulated ephrin-A1 conjugated liposomal nanoparticles inhibit tumor growth in lung cancer
title_sort	targeted delivery of let-7a microrna encapsulated ephrin-a1 conjugated liposomal nanoparticles inhibit tumor growth in lung cancer
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/3b823284bc2a49209ed6cb26cb79d7ec
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_version_	1718402642347032576

Targeted delivery of let-7a microRNA encapsulated ephrin-A1 conjugated liposomal nanoparticles inhibit tumor growth in lung cancer

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