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Folate-Targeted Multifunctional Amino Acid-Chitosan Nanoparticles for Improved Cancer Therapy

dc.contributor.authorGaspar, Vítor Manuel Abreu
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.accessioned2018-03-20T15:35:37Z
dc.date.available2018-03-20T15:35:37Z
dc.date.issued2015-02-01
dc.description.abstractPurpose Tumor targeting nanomaterials have potential for improving the efficiency of anti-tumoral therapeutics. However, the evaluation of their biological performance remains highly challenging. In this study we describe the synthesis of multifunctional nanoparticles decorated with folic acid-PEG and dual amino acid-modified chitosan (CM-PFA) complexed with DNA and their evaluation in organotypic 2D co-cultures of cancer-normal cells and also on 3D multicellular tumor spheroids models. Methods The physicochemical characterization of CM-PFA multifunctional carriers was performed by FTIR, 1H NMR and DLS. 2D co-culture models were established by using a 1:2 cancer-to-normal cell ratio. 3D organotypic tumor spheroids were assembled using micromolding technology for high throughput screening. Nanoparticle efficiency was evaluated by flow cytometry and confocal microscopy. Results The CM-PFA nanocarriers (126–176 nm) showed hemocompatibility and were internalized by target cells, achieving a 3.7 fold increase in gene expression. In vivo-mimicking 2D co-cultures confirmed a real affinity towards cancer cells and a negligible uptake in normal cells. The targeted nanoparticles penetrated into 3D spheroids to a higher extent than non-targeted nanocarriers. Also, CM-PFA-mediated delivery of p53 tumor suppressor promoted a decrease in tumor-spheroids volume. Conclusion These findings corroborate the improved efficiency of this delivery system and demonstrate its potential for application in cancer therapy.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationGaspar, V.M., Costa, E.C., Queiroz, J.A., Pichon, C., Sousa, F. e Correia, I.J. (2015) “Folate-Targeted Multifunctional Amino Acid-Chitosan Nanoparticles for Improved Cancer Therapy”, Pharmaceutical Research, Vol. 32(2): pp. 562-577pt_PT
dc.identifier.doi10.1007/s11095-014-1486-0pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.6/4666
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherSpringerpt_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://link.springer.com/article/10.1007%2Fs11095-014-1486-0pt_PT
dc.subjectCancer therapypt_PT
dc.subjectGene deliverypt_PT
dc.subjectTargeted nanoparticlespt_PT
dc.subject2D co-culturespt_PT
dc.subject3D tumor spheroidspt_PT
dc.titleFolate-Targeted Multifunctional Amino Acid-Chitosan Nanoparticles for Improved Cancer Therapypt_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.endPage577pt_PT
oaire.citation.startPage562pt_PT
oaire.citation.titlePharmaceutical Researchpt_PT
oaire.citation.volume32pt_PT
oaire.fundingStream5876-PPCDTI
oaire.fundingStream6820 - DCRRNI ID
oaire.fundingStreamFARH
person.familyNameGaspar
person.familyNameda Rocha Costa
person.familyNameQueiroz
person.familyNameSousa
person.familyNameJoaquim Sobreira Correia
person.givenNameVítor
person.givenNameElisabete Cristina
person.givenNameJoão
person.givenNameFani
person.givenNameIlídio
person.identifierUMbJ1KMAAAAJ
person.identifier.ciencia-id6F16-3640-73E3
person.identifier.ciencia-idB314-4CF0-6633
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.orcid0000-0002-0490-0095
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
person.identifier.scopus-author-id55805850100
person.identifier.scopus-author-id7003705645
person.identifier.scopus-author-id7005110268
person.identifier.scopus-author-id7003557499
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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