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RGD peptide-modified multifunctional dendrimer platform for drug encapsulation and targeted inhibition of cancer cells

2015Journal article Restricted access
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dc.contributor.authorHe, Xuedan
dc.contributor.authorAlves, Carla S.
dc.contributor.authorOliveira, Nilsa
dc.contributor.authorRodrigues, João
dc.contributor.authorZhu, Jingyi
dc.contributor.authorBányai, István
dc.contributor.authorTomás, Helena
dc.contributor.authorShi, Xiangyang
dc.date.accessioned2019-06-24T14:44:13Z
dc.date.available2019-06-24T14:44:13Z
dc.date.issued2015
dc.description.abstractDevelopment of multifunctional nanoscale drug-delivery systems for targeted cancer therapy still remains a great challenge. Here, we report the synthesis of cyclic arginine-glycine-aspartic acid (RGD) peptide-conjugated generation 5 (G5) poly(amidoamine) dendrimers for anticancer drug encapsulation and targeted therapy of cancer cells overexpressing αvβ3 integrins. In this study, amine-terminated G5 dendrimers were used as a platform to be sequentially modified with fluorescein isothiocyanate (FI) via a thiourea linkage and RGD peptide via a polyethylene glycol (PEG) spacer, followed by acetylation of the remaining dendrimer terminal amines. The developed multifunctional dendrimer platform (G5.NHAc-FI-PEG-RGD) was then used to encapsulate an anticancer drug doxorubicin (DOX). We show that approximately six DOX molecules are able to be encapsulated within each dendrimer platform. The formed complexes are water-soluble, stable, and able to release DOX in a sustained manner. One- and two-dimensional NMR techniques were applied to investigate the interaction between dendrimers and DOX, and the impact of the environmental pH on the release rate of DOX from the dendrimer/DOX complexes was also explored. Furthermore, cell biological studies demonstrate that the encapsulation of DOX within the G5.NHAc-FI-PEG-RGD dendrimers does not compromise the anticancer activity of DOX and that the therapeutic efficacy of the dendrimer/DOX complexes is solely related to the encapsulated DOX drug. Importantly, thanks to the role played by RGD-mediated targeting, the developed dendrimer/drug complexes are able to specifically target αvβ3 integrin-overexpressing cancer cells and display specific therapeutic efficacy to the target cells. The developed RGD peptide-targeted multifunctional dendrimers may thus be used as a versatile platform for targeted therapy of different types of αvβ3 integrin-overexpressing cancer cells.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationHe, X., Alves, C. S., Oliveira, N., Rodrigues, J., Zhu, J., Banyai, I., ... & Shi, X. (2015). RGD peptide-modified multifunctional dendrimer platform for drug encapsulation and targeted inhibition of cancer cells. Colloids and Surfaces B: Biointerfaces, 125, 82-89.pt_PT
dc.identifier.doi10.1016/j.colsurfb.2014.11.004pt_PT
dc.identifier.issn0927-7765
dc.identifier.urihttp://hdl.handle.net/10400.13/2425
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relationDENDIMAGE - Development of Novel Dendrimer-Based Nanoparticles for Dual Mode Computed Tomography and Magnetic Resonance Imaging of Tumors
dc.relationStrategic Project - UI 674 - 2011-2012
dc.subjectDendrimerspt_PT
dc.subjectRGD peptidept_PT
dc.subjectDexurobicinpt_PT
dc.subjectHost-guest interactionpt_PT
dc.subjectTargeted cancer therapypt_PT
dc.subject.pt_PT
dc.subjectFaculdade de Ciências Exatas e da Engenhariapt_PT
dc.subjectCentro de Química da Madeira
dc.titleRGD peptide-modified multifunctional dendrimer platform for drug encapsulation and targeted inhibition of cancer cellspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleDENDIMAGE - Development of Novel Dendrimer-Based Nanoparticles for Dual Mode Computed Tomography and Magnetic Resonance Imaging of Tumors
oaire.awardTitleStrategic Project - UI 674 - 2011-2012
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FCTM-NAN%2F1748%2F2012/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/PEst-OE%2FQUI%2FUI0674%2F2011/PT
oaire.citation.endPage89pt_PT
oaire.citation.startPage82pt_PT
oaire.citation.titleColloids and Surfaces B: Biointerfacespt_PT
oaire.citation.volume125pt_PT
oaire.fundingStream3599-PPCDT
oaire.fundingStream6817 - DCRRNI ID
person.familyNameAlves
person.familyNameRodrigues
person.familyNameTomás
person.familyNameShi
person.givenNameCarla Sophia
person.givenNameJoão
person.givenNameHelena
person.givenNameXiangyang
person.identifier556975
person.identifier.ciencia-idA81C-620E-DD6A
person.identifier.ciencia-id4D14-D31E-A8BE
person.identifier.ciencia-idBA11-1437-B948
person.identifier.orcid0000-0002-8891-5234
person.identifier.orcid0000-0003-4552-1953
person.identifier.orcid0000-0002-7856-2041
person.identifier.orcid0000-0001-6785-6645
person.identifier.ridB-6816-2008
person.identifier.ridE-5991-2010
person.identifier.ridA-1289-2007
person.identifier.scopus-author-id11438813200
person.identifier.scopus-author-id9233278800
person.identifier.scopus-author-id6508104177
person.identifier.scopus-author-id7402953116
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.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
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