In vivo therapeutic efficacy of TNF alpha silencing by folate-PEG-chitosan-DEAE/siRNA nanoparticles in arthritic mice

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dc.contributor.authorShi, Qin
dc.contributor.authorRondon-Cavanzo, Elsa-Patricia
dc.contributor.authorDalla Picola, Isadora Pfeifer [UNESP]
dc.contributor.authorTiera, Marcio Jose [UNESP]
dc.contributor.authorZhang, Xiaoling
dc.contributor.authorDai, Kerong
dc.contributor.authorBenabdoune, Houda Abir
dc.contributor.authorBenderdour, Mohamed
dc.contributor.authorFernandes, Julio Cesar
dc.contributor.institutionUniv Montreal
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionChinese Acad Sci
dc.contributor.institutionShanghai Jiao Tong Univ
dc.date.accessioned2018-11-26T17:44:44Z
dc.date.available2018-11-26T17:44:44Z
dc.date.issued2018-01-01
dc.description.abstractBackground: Tumor necrosis factor-alpha (TNF alpha), a pro-inflammatory cytokine, has been shown to play a role in the pathophysiology of rheumatoid arthritis. Silencing TNFa expression with small interfering RNA (siRNA) is a promising approach to treatment of the condition. Methods: Towards this end, our team has developed a modified chitosan (CH) nanocarrier, deploying folic acid, diethylethylamine (DEAE) and polyethylene glycol (PEG) (folate-PEG-CH-DEAE(15)). The gene carrier protects siRNA against nuclease destruction, its ligands facilitate siRNA uptake via cell surface receptors, and it provides improved solubility at neutral pH with transport of its load into target cells. In the present study, nanoparticles were prepared with siRNA-TNF alpha, DEAE, and folic acid-CH derivative. Nanoparticle size and zeta potential were verified by dynamic light scattering. Their TNF alpha-knockdown effects were tested in a murine collagen antibody-induced arthritis model. TNF alpha expression was examined along with measurements of various cartilage and bone turnover markers by performing histology and microcomputed tomography analysis. Results: We demonstrated that folate-PEG-CH-DEAE(15)/siRNA nanoparticles did not alter cell viability, and significantly decreased inflammation, as demonstrated by improved clinical scores and lower TNF alpha protein concentrations in target tissues. This siRNA nanocarrier also decreased articular cartilage destruction and bone loss. Conclusion: The results indicate that folate-PEG-CH-DEAE(15) nanoparticles are a safe and effective platform for nonviral gene delivery of siRNA, and their potential clinical applications warrant further investigation.en
dc.description.affiliationUniv Montreal, Orthoped Res Lab, Hop Sacre Coeur Montreal, Montreal, PQ, Canada
dc.description.affiliationUNESP Sao Paulo State Univ, Dept Chem & Environm Sci, Sao Jose Do Rio Preto, Brazil
dc.description.affiliationChinese Acad Sci, Orthoped Cellular & Mol Biol Labs, Inst Hlth Sci, Shanghai, Peoples R China
dc.description.affiliationShanghai Jiao Tong Univ, Sch Med, Shanghai, Peoples R China
dc.description.affiliationShanghai Jiao Tong Univ, Dept Orthoped, Peoples Hosp 9, Sch Med, Shanghai, Peoples R China
dc.description.affiliationUnespUNESP Sao Paulo State Univ, Dept Chem & Environm Sci, Sao Jose Do Rio Preto, Brazil
dc.description.sponsorshipScience and Technology Commission of Shanghai Municipality
dc.description.sponsorshipMinistere de l'Economie, de la Science et de l'Innovation du Quebec (Programme de soutien a la recherche [PSR], volet 4: Soutien a des initiatives internationales de recherche et d'innovation [SIIRI])
dc.description.sponsorshipCanadian Institutes of Health Research
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipIdScience and Technology Commission of Shanghai Municipality: 16430723500
dc.description.sponsorshipIdCanadian Institutes of Health Research: CCM 104888
dc.description.sponsorshipIdCNPq: 407499/2013-0
dc.format.extent387-402
dc.identifierhttp://dx.doi.org/10.2147/IJN.S146942
dc.identifier.citationInternational Journal Of Nanomedicine. Albany: Dove Medical Press Ltd, v. 13, p. 387-402, 2018.
dc.identifier.doi10.2147/IJN.S146942
dc.identifier.issn1178-2013
dc.identifier.lattes8796747160088337
dc.identifier.urihttp://hdl.handle.net/11449/163729
dc.identifier.wosWOS:000422629800001
dc.language.isoeng
dc.publisherDove Medical Press Ltd
dc.relation.ispartofInternational Journal Of Nanomedicine
dc.rights.accessRightsAcesso restrito
dc.sourceWeb of Science
dc.subjectarthritis
dc.subjectinflammation
dc.subjectsiRNA
dc.subjectTNF alpha
dc.subjectnanoparticles
dc.subjectchitosan
dc.titleIn vivo therapeutic efficacy of TNF alpha silencing by folate-PEG-chitosan-DEAE/siRNA nanoparticles in arthritic miceen
dc.typeArtigo
dcterms.rightsHolderDove Medical Press Ltd
unesp.author.lattes8796747160088337

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