Polymeric nanoparticle-based delivery of microRNA-199a-3p inhibits proliferation and growth of osteosarcoma cells

Linlin Zhang,1,2,* Arun K lyer,3,4,* Xiaoqian Yang,1 Eisuke Kobayashi,1 Yuqi Guo,1,2 Henry Mankin,1 Francis J Hornicek,1 Mansoor M Amiji,3 Zhenfeng Duan1 1Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA; 2Depa...

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Autores principales:	Zhang L, Iyer AK, Yang X, Kobayashi E, Guo Y, Mankin H, Hornicek FJ, Amiji MM, Duan Z
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/1cfddf658c4c4f44a0bff329effba70f
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spelling	oai:doaj.org-article:1cfddf658c4c4f44a0bff329effba70f2021-12-02T07:43:10ZPolymeric nanoparticle-based delivery of microRNA-199a-3p inhibits proliferation and growth of osteosarcoma cells1178-2013https://doaj.org/article/1cfddf658c4c4f44a0bff329effba70f2015-04-01T00:00:00Zhttp://www.dovepress.com/polymeric-nanoparticle-based-delivery-of-microrna-199a-3p-inhibits-pro-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Linlin Zhang,1,2,* Arun K lyer,3,4,* Xiaoqian Yang,1 Eisuke Kobayashi,1 Yuqi Guo,1,2 Henry Mankin,1 Francis J Hornicek,1 Mansoor M Amiji,3 Zhenfeng Duan1 1Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA; 2Department of Pathology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 3Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, Massachusetts, USA; 4Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, USA *These authors contributed equally to this work Abstract: Our prior screening of microRNAs (miRs) identified that miR-199a-3p expression is reduced in osteosarcoma cells, one of the most common types of bone tumor. miR-199a-3p exhibited functions of tumor cell growth inhibition, suggesting the potential application of miR-199a-3p as an anticancer agent. In the study reported here, we designed and developed a lipid-modified dextran-based polymeric nanoparticle platform for encapsulation of miRs, and determined the efficiency and efficacy of delivering miR-199a-3p into osteosarcoma cells. In addition, another potent miR, let-7a, which also displayed tumor suppressive ability, was selected as a candidate miR for evaluation. Fluorescence microscopy studies and real-time polymerase chain reaction results showed that dextran nanoparticles could deliver both miR-199a-3p and let-7a into osteosarcoma cell lines (KHOS and U-2OS) successfully. Western blotting analysis and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays demonstrated that dextran nanoparticles loaded with miRs could efficiently downregulate the expression of target proteins and effectively inhibit the growth and proliferation of osteosarcoma cells. These results demonstrate that a lipid-modified dextran-based polymeric nanoparticle platform may be an effective nonviral carrier for potential miR-based anticancer therapeutics. Keywords: bone tumor, dextran nanoparticles, miR-199a-3p, let-7a, RNAiZhang LIyer AKYang XKobayashi EGuo YMankin HHornicek FJAmiji MMDuan ZDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 2913-2924 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Zhang L Iyer AK Yang X Kobayashi E Guo Y Mankin H Hornicek FJ Amiji MM Duan Z Polymeric nanoparticle-based delivery of microRNA-199a-3p inhibits proliferation and growth of osteosarcoma cells
description	Linlin Zhang,1,2,* Arun K lyer,3,4,* Xiaoqian Yang,1 Eisuke Kobayashi,1 Yuqi Guo,1,2 Henry Mankin,1 Francis J Hornicek,1 Mansoor M Amiji,3 Zhenfeng Duan1 1Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA; 2Department of Pathology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 3Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, Massachusetts, USA; 4Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, USA *These authors contributed equally to this work Abstract: Our prior screening of microRNAs (miRs) identified that miR-199a-3p expression is reduced in osteosarcoma cells, one of the most common types of bone tumor. miR-199a-3p exhibited functions of tumor cell growth inhibition, suggesting the potential application of miR-199a-3p as an anticancer agent. In the study reported here, we designed and developed a lipid-modified dextran-based polymeric nanoparticle platform for encapsulation of miRs, and determined the efficiency and efficacy of delivering miR-199a-3p into osteosarcoma cells. In addition, another potent miR, let-7a, which also displayed tumor suppressive ability, was selected as a candidate miR for evaluation. Fluorescence microscopy studies and real-time polymerase chain reaction results showed that dextran nanoparticles could deliver both miR-199a-3p and let-7a into osteosarcoma cell lines (KHOS and U-2OS) successfully. Western blotting analysis and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays demonstrated that dextran nanoparticles loaded with miRs could efficiently downregulate the expression of target proteins and effectively inhibit the growth and proliferation of osteosarcoma cells. These results demonstrate that a lipid-modified dextran-based polymeric nanoparticle platform may be an effective nonviral carrier for potential miR-based anticancer therapeutics. Keywords: bone tumor, dextran nanoparticles, miR-199a-3p, let-7a, RNAi
format	article
author	Zhang L Iyer AK Yang X Kobayashi E Guo Y Mankin H Hornicek FJ Amiji MM Duan Z
author_facet	Zhang L Iyer AK Yang X Kobayashi E Guo Y Mankin H Hornicek FJ Amiji MM Duan Z
author_sort	Zhang L
title	Polymeric nanoparticle-based delivery of microRNA-199a-3p inhibits proliferation and growth of osteosarcoma cells
title_short	Polymeric nanoparticle-based delivery of microRNA-199a-3p inhibits proliferation and growth of osteosarcoma cells
title_full	Polymeric nanoparticle-based delivery of microRNA-199a-3p inhibits proliferation and growth of osteosarcoma cells
title_fullStr	Polymeric nanoparticle-based delivery of microRNA-199a-3p inhibits proliferation and growth of osteosarcoma cells
title_full_unstemmed	Polymeric nanoparticle-based delivery of microRNA-199a-3p inhibits proliferation and growth of osteosarcoma cells
title_sort	polymeric nanoparticle-based delivery of microrna-199a-3p inhibits proliferation and growth of osteosarcoma cells
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/1cfddf658c4c4f44a0bff329effba70f
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Polymeric nanoparticle-based delivery of microRNA-199a-3p inhibits proliferation and growth of osteosarcoma cells

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