Nanoscale polysaccharide derivative as an AEG-1 siRNA carrier for effective osteosarcoma therapy

Fen Wang,1,* Jia-Dong Pang,2,* Lei-lei Huang,1 Ran Wang,1 Dan Li,3 Kang Sun,4 Lian-tang Wang,1,* Li-Ming Zhang2,* 1Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, 2PCFM Lab and GDHPPC Lab, School of Materials Science and Engineering, Sun Yat-sen University, Guangzh...

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Autores principales:	Wang F, Pang J, Huang L, Wang R, Li D, Sun K, Wang L, Zhang L
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	Chitosan Gene delivery AEG-1 siRNA Osteosarcoma Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/016b4b27983349cc87b721699576d15c
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spelling	oai:doaj.org-article:016b4b27983349cc87b721699576d15c2021-12-02T00:23:54ZNanoscale polysaccharide derivative as an AEG-1 siRNA carrier for effective osteosarcoma therapy1178-2013https://doaj.org/article/016b4b27983349cc87b721699576d15c2018-02-01T00:00:00Zhttps://www.dovepress.com/nanoscale-polysaccharide-derivative-as-an-aeg-1-sirna-carrier-for-effe-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Fen Wang,1,* Jia-Dong Pang,2,* Lei-lei Huang,1 Ran Wang,1 Dan Li,3 Kang Sun,4 Lian-tang Wang,1,* Li-Ming Zhang2,* 1Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, 2PCFM Lab and GDHPPC Lab, School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou, 3Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, 4School of Engineering, Sun Yat-sen University, Guangzhou, China *These authors contributed equally to this work Background: Nanomedicine, which is the application of nanotechnology in medicine to make medical diagnosis and treatment more accurate, has great potential for precision medicine. Despite some improvements in nanomedicine, the lack of efficient and low-toxic vectors remains a major obstacle. Objective: The aim of this study was to prepare an efficient and low-toxic vector which could deliver astrocyte elevated gene-1 (AEG-1) small interfering RNA (siRNA; siAEG-1) into osteosarcoma cells effectively and silence the targeted gene both in vitro and in vivo. Materials and methods: We prepared a novel polysaccharide derivative by click conjugation of azidized chitosan with propargyl focal point poly (L-lysine) dendrons (PLLD) and subsequent coupling with folic acid (FA; Cs-g-PLLD-FA). We confirmed the complexation of siAEG-1and Cs-g-PLLD or Cs-g-PLLD-FA by gel retardation assay. We examined the cell cytotoxicity, cell uptake, cell proliferation and invasion abilities of Cs-g-PLLD-FA/siAEG-1 in osteosarcoma cells. In osteosarcoma 143B cells tumor-bearing mice models, we established the therapeutic efficacy and safety of Cs-g-PLLD-FA/siAEG-1. Results: Cs-g-PLLD-FA could completely encapsulate siAEG-1 and showed low cytotoxicity in osteosarcoma cells and tumour-bearing mice. The Cs-g-PLLD-FA/siAEG-1 nanocomplexes were capable of transferring siAEG-1 into osteosarcoma cells efficiently, and the knockdown of AEG-1 resulted in the inhibition of tumour cell proliferation and invasion. In addition, caudal vein injecting of Cs-g-PLLD-FA/siAEG-1 complexes inhibited tumor growth and lung metastasis in tumor-bearing mice by silencing AEG-1 and regulating MMP-2/9. Conclusion: In summary, Cs-g-PLLD-FA nanoparticles are a promising system for the effective delivery of AEG-1 siRNA for treating osteosarcoma. Keywords: chitosan, gene delivery, astrocyte elevated gene-1, small interfering RNA, osteosarcomaWang FPang JHuang LWang RLi DSun KWang LZhang LDove Medical PressarticleChitosanGene deliveryAEG-1 siRNAOsteosarcomaMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 857-875 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Chitosan Gene delivery AEG-1 siRNA Osteosarcoma Medicine (General) R5-920
spellingShingle	Chitosan Gene delivery AEG-1 siRNA Osteosarcoma Medicine (General) R5-920 Wang F Pang J Huang L Wang R Li D Sun K Wang L Zhang L Nanoscale polysaccharide derivative as an AEG-1 siRNA carrier for effective osteosarcoma therapy
description	Fen Wang,1,* Jia-Dong Pang,2,* Lei-lei Huang,1 Ran Wang,1 Dan Li,3 Kang Sun,4 Lian-tang Wang,1,* Li-Ming Zhang2,* 1Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, 2PCFM Lab and GDHPPC Lab, School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou, 3Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, 4School of Engineering, Sun Yat-sen University, Guangzhou, China *These authors contributed equally to this work Background: Nanomedicine, which is the application of nanotechnology in medicine to make medical diagnosis and treatment more accurate, has great potential for precision medicine. Despite some improvements in nanomedicine, the lack of efficient and low-toxic vectors remains a major obstacle. Objective: The aim of this study was to prepare an efficient and low-toxic vector which could deliver astrocyte elevated gene-1 (AEG-1) small interfering RNA (siRNA; siAEG-1) into osteosarcoma cells effectively and silence the targeted gene both in vitro and in vivo. Materials and methods: We prepared a novel polysaccharide derivative by click conjugation of azidized chitosan with propargyl focal point poly (L-lysine) dendrons (PLLD) and subsequent coupling with folic acid (FA; Cs-g-PLLD-FA). We confirmed the complexation of siAEG-1and Cs-g-PLLD or Cs-g-PLLD-FA by gel retardation assay. We examined the cell cytotoxicity, cell uptake, cell proliferation and invasion abilities of Cs-g-PLLD-FA/siAEG-1 in osteosarcoma cells. In osteosarcoma 143B cells tumor-bearing mice models, we established the therapeutic efficacy and safety of Cs-g-PLLD-FA/siAEG-1. Results: Cs-g-PLLD-FA could completely encapsulate siAEG-1 and showed low cytotoxicity in osteosarcoma cells and tumour-bearing mice. The Cs-g-PLLD-FA/siAEG-1 nanocomplexes were capable of transferring siAEG-1 into osteosarcoma cells efficiently, and the knockdown of AEG-1 resulted in the inhibition of tumour cell proliferation and invasion. In addition, caudal vein injecting of Cs-g-PLLD-FA/siAEG-1 complexes inhibited tumor growth and lung metastasis in tumor-bearing mice by silencing AEG-1 and regulating MMP-2/9. Conclusion: In summary, Cs-g-PLLD-FA nanoparticles are a promising system for the effective delivery of AEG-1 siRNA for treating osteosarcoma. Keywords: chitosan, gene delivery, astrocyte elevated gene-1, small interfering RNA, osteosarcoma
format	article
author	Wang F Pang J Huang L Wang R Li D Sun K Wang L Zhang L
author_facet	Wang F Pang J Huang L Wang R Li D Sun K Wang L Zhang L
author_sort	Wang F
title	Nanoscale polysaccharide derivative as an AEG-1 siRNA carrier for effective osteosarcoma therapy
title_short	Nanoscale polysaccharide derivative as an AEG-1 siRNA carrier for effective osteosarcoma therapy
title_full	Nanoscale polysaccharide derivative as an AEG-1 siRNA carrier for effective osteosarcoma therapy
title_fullStr	Nanoscale polysaccharide derivative as an AEG-1 siRNA carrier for effective osteosarcoma therapy
title_full_unstemmed	Nanoscale polysaccharide derivative as an AEG-1 siRNA carrier for effective osteosarcoma therapy
title_sort	nanoscale polysaccharide derivative as an aeg-1 sirna carrier for effective osteosarcoma therapy
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/016b4b27983349cc87b721699576d15c
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Nanoscale polysaccharide derivative as an AEG-1 siRNA carrier for effective osteosarcoma therapy

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