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Nanoparticle mediated delivery of pure P53 supercoiled plasmid DNA for gene therapy

2011-08-12Journal article Restricted access
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dc.contributor.authorGaspar, Vítor Manuel Abreu
dc.contributor.authorCorreia, Ilídio
dc.contributor.authorSousa, Ângela
dc.contributor.authorSilva, Filomena
dc.contributor.authorPaquete, Catarina
dc.contributor.authorQueiroz, João
dc.contributor.authorSousa, Fani
dc.date.accessioned2018-03-19T11:00:37Z
dc.date.available2018-03-19T11:00:37Z
dc.date.issued2011-08-12
dc.description.abstractThe translation of non-viral gene replacement therapies for cancer into clinical application is currently hindered due to known issues associated with the effectiveness of plasmid DNA (pDNA) expression vectors and the production of gene delivery vehicles. Herein we report an integrative approach established on the synthesis of nanoparticulated carriers, in association with the supercoiled (sc) isoform purification of a p53 tumor suppressor encoding plasmid, to improve both delivery and transfection. An arginine-based chromatographic matrix with specific recognition for the different topoisoforms was used to completely isolate the biologically active sc pDNA. Our findings showed that the sc topoisoform is recovered under mild conditions with high purity and structural stability. In addition, to further enhance protection and transfection efficiency, the naked sc pDNA was encapsulated within chitosan nanoparticles by ionotropic gelation. The mild conditions for particle synthesis used in the former technique allowed the attainment of a high encapsulation efficiency for sc pDNA (> 75%). Moreover, in vitro transfection experiments confirmed the reinstatement of the p53 protein expression and most importantly, the sc pDNA transfected cells exhibited the highest p53 expression levels when compared to other formulations. Overall, given the fact that sc pDNA topoisoform indeed enhances transgene expression rates this approach might have a profound impact on the development of a sustained nucleic acid-based therapy for cancer.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationGaspar, V.M., Correia, I.J., Sousa, A., Silva, F., Paquete, C.M., Queiroz, J.A. e Sousa, F. (2011) “Nanoparticle mediated delivery of pure P53 supercoiled plasmid DNA for gene therapy”, Journal of Controlled Release, Vol. 156 (2), pp. 212-222pt_PT
dc.identifier.doi10.1016/j.jconrel.2011.08.007pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.6/4631
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relationIsolation and Purification of Plasmid DNA for Cancer Therapy
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/pii/S016836591100575Xpt_PT
dc.subjectGene therapypt_PT
dc.subjectNanoparticlespt_PT
dc.subjectp53 Tumor suppressorpt_PT
dc.subjectSupercoiled plasmid DNApt_PT
dc.titleNanoparticle mediated delivery of pure P53 supercoiled plasmid DNA for gene therapypt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleIsolation and Purification of Plasmid DNA for Cancer Therapy
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FEME-TME%2F103375%2F2008/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876-PPCDTI/PTDC%2FEBB-BIO%2F114320%2F2009/PT
oaire.citation.endPage222pt_PT
oaire.citation.startPage212pt_PT
oaire.citation.titleJournal of Controlled Releasept_PT
oaire.citation.volume156pt_PT
oaire.fundingStream3599-PPCDT
oaire.fundingStream5876-PPCDTI
person.familyNameGaspar
person.familyNameJoaquim Sobreira Correia
person.familyNameSousa
person.familyNamePaquete
person.familyNameQueiroz
person.familyNameSousa
person.givenNameVítor
person.givenNameIlídio
person.givenNameÂngela
person.givenNameCatarina
person.givenNameJoão
person.givenNameFani
person.identifierUMbJ1KMAAAAJ
person.identifier817754
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person.identifier.ciencia-idA01E-576D-43B7
person.identifier.ciencia-id931E-B66D-E341
person.identifier.ciencia-id991D-2E13-A840
person.identifier.orcid0000-0002-0372-2493
person.identifier.orcid0000-0003-1613-9675
person.identifier.orcid0000-0001-9155-7581
person.identifier.orcid0000-0002-1511-3732
person.identifier.orcid0000-0002-3096-8325
person.identifier.orcid0000-0001-9996-2194
person.identifier.ridB-1602-2017
person.identifier.ridA-6615-2016
person.identifier.ridL-3104-2014
person.identifier.ridA-2014-2017
person.identifier.scopus-author-id36968590900
person.identifier.scopus-author-id7003557499
person.identifier.scopus-author-id24330268800
person.identifier.scopus-author-id6507206247
person.identifier.scopus-author-id7003705645
person.identifier.scopus-author-id7005110268
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.embargofctCopyright cedido à editora no momento da publicaçãopt_PT
rcaap.rightsclosedAccesspt_PT
rcaap.typearticlept_PT
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