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Bioreducible poly(2-ethyl-2-oxazoline)–PLA–PEI-SS triblock copolymer micelles for co-delivery of DNA minicircles and Doxorubicin

2015-07-13Journal article Restricted access
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dc.contributor.authorGaspar, Vítor Manuel Abreu
dc.contributor.authorBaril, Patrick
dc.contributor.authorCosta, Elisabete C.
dc.contributor.authorDiogo, Duarte Miguel de Melo
dc.contributor.authorFoucher, Frédéric
dc.contributor.authorQueiroz, João
dc.contributor.authorSousa, Fani
dc.contributor.authorPichon, Chantal
dc.contributor.authorCorreia, I.J.
dc.date.accessioned2018-03-21T09:34:04Z
dc.date.available2018-03-21T09:34:04Z
dc.date.issued2015-07-13
dc.description.abstractThe co-delivery of minicircle DNA (mcDNA) and small anti-cancer drugs via stimuli-sensitive nanocarriers is a promising approach for combinatorial cancer therapy. However, the simultaneous loading of drugs and DNA in nanosized delivery systems is remarkably challenging. In this study we describe the synthesis of triblock copolymer micelles based on poly(2-ethyl-2-oxazoline)–poly(L-lactide) grafted with bioreducible polyethylenimine (PEOz–PLA-g–PEI-SS) for co-delivery of supercoiled (sc) mcDNA vectors and Doxorubicin (Dox). These amphiphilic carriers take advantage of non-fouling oxazolines to confer biological stability, of PLA to provide a hydrophobic core for drug encapsulation and of bioreducible PEI-SS to provide mcDNA complexation and an on-demand stimuli-responsive release. The obtained results show that mcDNA-loaded micelleplexes penetrate into in vitro tumor spheroid models with specific kinetics and exhibit a higher gene expression when compared to non-bioreducible nanocarriers. Moreover, in vivo bioluminescence imaging showed that gene expression is detected up to 8 days following mcDNA-micelles intratumoral administration. Furthermore, drug–gene co-delivery in PEOz–PLA-g–PEI-SS carriers was verified by successful encapsulation of both Dox and mcDNA with high efficacy. Moreover, dual-loaded micelleplexes presented significant uptake and a cytotoxic effect in 2D cultures of cancer cells. The co-delivery of mcDNA-Dox to B16F10-Luciferase tumor bearing mice resulted in a reduction in tumor volume and cancer cells viability. Overall, such findings indicate that bioreducible triblock micelles are efficient for focal delivery in vivo and have potential for future application in combinatorial DNA-drug therapy.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationGaspar, V.M., Baril, P., Costa, E.C., De Melo-Diogo, D., Foucher, F., Queiroz, J.A., Sousa, F., Pichon, C. e Correia, I.J. (2015) “Bioreducible poly(2-ethyl-2-oxazoline)-PLA-PEI-SS triblock copolymer micelles for co-delivery of DNA minicircles and doxorubicin”, Journal of Controlled Release, Vol. 213, pp.175-191pt_PT
dc.identifier.doi10.1016/j.jconrel.2015.07.011pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.6/4675
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.relationMULTIFUNCTIONAL GRAPHENE-OXIDE NANOCARRIERS FOR DRUG DELIVERY AND PHOTOTHERMAL THERAPY OF LUNG CANCER
dc.relation3D multicellular spheroids as high throughput platforms to screen novel combinatory therapies for treatment of pancreatic cancer
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/pii/S0168365915300249?via%3Dihubpt_PT
dc.subjectBioreducible micellespt_PT
dc.subjectMinicircle DNApt_PT
dc.subjectCo-deliverypt_PT
dc.subjectChemotherapeuticspt_PT
dc.subjectCancer therapypt_PT
dc.titleBioreducible poly(2-ethyl-2-oxazoline)–PLA–PEI-SS triblock copolymer micelles for co-delivery of DNA minicircles and Doxorubicinpt_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.awardTitleMULTIFUNCTIONAL GRAPHENE-OXIDE NANOCARRIERS FOR DRUG DELIVERY AND PHOTOTHERMAL THERAPY OF LUNG CANCER
oaire.awardTitle3D multicellular spheroids as high throughput platforms to screen novel combinatory therapies for treatment of pancreatic cancer
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.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F103506%2F2014/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F103507%2F2014/PT
oaire.citation.endPage191pt_PT
oaire.citation.startPage175pt_PT
oaire.citation.titleJournal of Controlled Releasept_PT
oaire.citation.volume213pt_PT
oaire.fundingStream5876-PPCDTI
oaire.fundingStream6820 - DCRRNI ID
oaire.fundingStreamFARH
person.familyNameGaspar
person.familyNameBARIL
person.familyNameda Rocha Costa
person.familyNameMiguel de Melo Diogo
person.familyNameQueiroz
person.familyNameSousa
person.familyNameJoaquim Sobreira Correia
person.givenNameVítor
person.givenNamePatrick
person.givenNameElisabete Cristina
person.givenNameDuarte
person.givenNameJoão
person.givenNameFani
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project.funder.identifierhttp://doi.org/10.13039/501100001871
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project.funder.nameFundação para a Ciência e a Tecnologia
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rcaap.embargofctCopyright cedido à editora no momento da publicaçãopt_PT
rcaap.rightsclosedAccesspt_PT
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