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Poly(2-ethyl-2-oxazoline)–PLA-g–PEI amphiphilic triblock micelles for co-delivery of minicircle DNA and chemotherapeutics

2014-06-28Journal article Restricted access
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dc.contributor.authorGaspar, Vítor Manuel Abreu
dc.contributor.authorGonçalves, Cristine
dc.contributor.authorDiogo, Duarte Miguel de Melo
dc.contributor.authorCosta, Elisabete C.
dc.contributor.authorQueiroz, João
dc.contributor.authorPichon, Chantal
dc.contributor.authorSousa, Fani
dc.contributor.authorCorreia, Ilídio Joaquim Sobreira
dc.date.accessioned2018-03-20T11:20:24Z
dc.date.available2018-03-20T11:20:24Z
dc.date.issued2014-06-28
dc.description.abstractThe design of nanocarriers for the delivery of drugs and nucleic-acids remains a very challenging goal due to their physicochemical differences. In addition, the reported accelerated clearance and immune response of pegylated nanomedicines highlight the necessity to develop carriers using new materials. Herein, we describe the synthesis of amphiphilic triblock poly(2-ethyl-2-oxazoline)–PLA-g–PEI (PEOz–PLA-g–PEI) micelles for the delivery of minicircle DNA (mcDNA) vectors. In this copolymer the generally used PEG moieties are replaced by the biocompatible PEOz polymer backbone that assembles the hydrophilic shell. The obtained results show that amphiphilic micelles have low critical micellar concentration, are hemocompatible and exhibit stability upon incubation in serum. The uptake in MCF-7 cells was efficient and the nanocarriers achieved 2.7 fold higher expression than control particles. Moreover, mcDNA-loaded micelleplexes penetrated into 3D multicellular spheroids and promoted widespread gene expression. Additionally, to prove the concept of co-delivery, mcDNA and doxorubicin (Dox) were simultaneously encapsulated in PEOz–PLA-g–PEI carriers, with high efficiency. Dox–mcDNA micelleplexes exhibited extensive cellular uptake and demonstrated anti-tumoral activity. These findings led us to conclude that this system has a potential not only for the delivery of novel mcDNA vectors, but also for the co-delivery of drug–mcDNA combinations without PEG functionalization.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationGaspar, V.M., Gonçalves, C., De Melo-Diogo, D., Costa, E.C., Queiroz, J.A., Pinchon, C., Sousa, F. e Correia, I.J. (2014) “Poly (2-ethyl-2-oxazoline)-PLA-g-PEI Amphiphilic Triblock Micelles for Co-delivery of Minicircle DNA and Chemotherapeutics”, Journal of Controlled Release, Vol. 189, pp. 90-104pt_PT
dc.identifier.doi10.1016/j.jconrel.2014.06.040pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.6/4653
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relationIsolation and Purification of Plasmid DNA for Cancer Therapy
dc.relationStrategic Project - UI 709 - 2011-2012
dc.relationBIOSYNTHESIS AND PURIFICATION OF MINICIRCLE DNA FOR APPLICATION IN DIABETES CELL-SPECIFIC GENE THERAPY
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/pii/S0168365914004490?via%3Dihub#!pt_PT
dc.subjectCo-deliverypt_PT
dc.subjectMinicircle DNApt_PT
dc.subjectAnti-tumoral drugspt_PT
dc.subjectMicellar carrierspt_PT
dc.subjectCancer therapypt_PT
dc.titlePoly(2-ethyl-2-oxazoline)–PLA-g–PEI amphiphilic triblock micelles for co-delivery of minicircle DNA and chemotherapeuticspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleIsolation and Purification of Plasmid DNA for Cancer Therapy
oaire.awardTitleStrategic Project - UI 709 - 2011-2012
oaire.awardTitleBIOSYNTHESIS AND PURIFICATION OF MINICIRCLE DNA FOR APPLICATION IN DIABETES CELL-SPECIFIC GENE THERAPY
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876-PPCDTI/PTDC%2FEBB-BIO%2F114320%2F2009/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6820 - DCRRNI ID/PEst-C%2FSAU%2FUI0709%2F2011/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/FARH/SFRH%2FBD%2F80402%2F2011/PT
oaire.citation.endPage104pt_PT
oaire.citation.startPage90pt_PT
oaire.citation.titleJournal of Controlled Releasept_PT
oaire.citation.volume189pt_PT
oaire.fundingStream5876-PPCDTI
oaire.fundingStream6820 - DCRRNI ID
oaire.fundingStreamFARH
person.familyNameGaspar
person.familyNameMiguel de Melo Diogo
person.familyNameda Rocha Costa
person.familyNameQueiroz
person.familyNameSousa
person.familyNameJoaquim Sobreira Correia
person.givenNameVítor
person.givenNameDuarte
person.givenNameElisabete Cristina
person.givenNameJoão
person.givenNameFani
person.givenNameIlídio
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person.identifier.ciencia-id931E-B66D-E341
person.identifier.ciencia-id991D-2E13-A840
person.identifier.ciencia-idF610-7373-DC81
person.identifier.orcid0000-0002-0372-2493
person.identifier.orcid0000-0001-9984-3603
person.identifier.orcid0000-0002-0490-0095
person.identifier.orcid0000-0002-3096-8325
person.identifier.orcid0000-0001-9996-2194
person.identifier.orcid0000-0003-1613-9675
person.identifier.ridB-1602-2017
person.identifier.ridL-3104-2014
person.identifier.ridA-2014-2017
person.identifier.scopus-author-id36968590900
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person.identifier.scopus-author-id55805850100
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project.funder.identifierhttp://doi.org/10.13039/501100001871
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
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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