Counteracting the effect of leukemia exosomes by antiangiogenic gold nanoparticles

Catarina Roma-Rodrigues, Alexandra R Fernandes, Pedro V BaptistaUCIBIO, Departamento de Ciências da Vida, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, Campus de Caparica, Caparica 2829-516, PortugalCorrespondence: Alexandra R Fernandes; Pedro V BaptistaUCIBIO,...

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Autores principales: Roma-Rodrigues C, Fernandes AR, Baptista PV
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Publicado: Dove Medical Press 2019
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spelling oai:doaj.org-article:6c1e8356c1824deab5145fc9f5c1203a2021-12-02T09:23:10ZCounteracting the effect of leukemia exosomes by antiangiogenic gold nanoparticles1178-2013https://doaj.org/article/6c1e8356c1824deab5145fc9f5c1203a2019-08-01T00:00:00Zhttps://www.dovepress.com/counteracting-the-effect-of-leukemia-exosomes-by-antiangiogenic-gold-n-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Catarina Roma-Rodrigues, Alexandra R Fernandes, Pedro V BaptistaUCIBIO, Departamento de Ciências da Vida, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, Campus de Caparica, Caparica 2829-516, PortugalCorrespondence: Alexandra R Fernandes; Pedro V BaptistaUCIBIO, Departamento de Ciências da Vida, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, Campus de Caparica, Caparica 2829-516, PortugalTel +351 21 294 8530Fax +351 21 294 8530Email ma.fernandes@fct.unl.pt pmvb@fct.unl.ptPurpose: Progression of chronic myeloid leukemia (CML) is frequently associated with increased angiogenesis at the bone marrow mediated by exosomes. The capability of gold nanoparticles (AuNPs) functionalized with antiangiogenic peptides to hinder the formation of new blood vessels has been demonstrated in a chorioallantoic membrane (CAM) model.Methods: Exosomes of K562 CML cell line were isolated and their angiogenic effect assessed in a CAM model. AuNPs functionalized with antiangiogenic peptides were used to block the angiogenic effect of CML-derived exosomes, assessed by evaluation of expression levels of key modulators involved in angiogenic pathways - VEGFA, VEGFR1 (also known as FLT1) and IL8.Results: Exosomes isolated from K562 cells promoted the doubling of newly formed vessels associated with the increase of VEGFR1 expression. This is a concentration and time-dependent effect. The AuNPs functionalized with antiangiogenic peptides were capable to block the angiogenic effect by modulating VEGFR1 associated pathway.Conclusion: Exosomes derived from blast cells are capable to trigger (neo)-angiogenesis, a key factor for the progression and spreading of cancer, in particular in CML. AuNPs functionalized with specific antiangiogenic peptides are capable to block the effect of the exosomes produced by malignant cells via modulation of the intrinsic VEGFR pathway. Together, these data highlight the potential of nanomedicine-based strategies against cancer proliferation.Keywords: chronic myeloid leukemia, exosomes, chorioallantoic membrane, gold nanoparticles, angiogenesisRoma-Rodrigues CFernandes ARBaptista PVDove Medical PressarticleChronic myeloid leukemiaexosomeschorioallantoic membranegold nanoparticlesangiogenesisMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 6843-6854 (2019)
institution DOAJ
collection DOAJ
language EN
topic Chronic myeloid leukemia
exosomes
chorioallantoic membrane
gold nanoparticles
angiogenesis
Medicine (General)
R5-920
spellingShingle Chronic myeloid leukemia
exosomes
chorioallantoic membrane
gold nanoparticles
angiogenesis
Medicine (General)
R5-920
Roma-Rodrigues C
Fernandes AR
Baptista PV
Counteracting the effect of leukemia exosomes by antiangiogenic gold nanoparticles
description Catarina Roma-Rodrigues, Alexandra R Fernandes, Pedro V BaptistaUCIBIO, Departamento de Ciências da Vida, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, Campus de Caparica, Caparica 2829-516, PortugalCorrespondence: Alexandra R Fernandes; Pedro V BaptistaUCIBIO, Departamento de Ciências da Vida, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, Campus de Caparica, Caparica 2829-516, PortugalTel +351 21 294 8530Fax +351 21 294 8530Email ma.fernandes@fct.unl.pt pmvb@fct.unl.ptPurpose: Progression of chronic myeloid leukemia (CML) is frequently associated with increased angiogenesis at the bone marrow mediated by exosomes. The capability of gold nanoparticles (AuNPs) functionalized with antiangiogenic peptides to hinder the formation of new blood vessels has been demonstrated in a chorioallantoic membrane (CAM) model.Methods: Exosomes of K562 CML cell line were isolated and their angiogenic effect assessed in a CAM model. AuNPs functionalized with antiangiogenic peptides were used to block the angiogenic effect of CML-derived exosomes, assessed by evaluation of expression levels of key modulators involved in angiogenic pathways - VEGFA, VEGFR1 (also known as FLT1) and IL8.Results: Exosomes isolated from K562 cells promoted the doubling of newly formed vessels associated with the increase of VEGFR1 expression. This is a concentration and time-dependent effect. The AuNPs functionalized with antiangiogenic peptides were capable to block the angiogenic effect by modulating VEGFR1 associated pathway.Conclusion: Exosomes derived from blast cells are capable to trigger (neo)-angiogenesis, a key factor for the progression and spreading of cancer, in particular in CML. AuNPs functionalized with specific antiangiogenic peptides are capable to block the effect of the exosomes produced by malignant cells via modulation of the intrinsic VEGFR pathway. Together, these data highlight the potential of nanomedicine-based strategies against cancer proliferation.Keywords: chronic myeloid leukemia, exosomes, chorioallantoic membrane, gold nanoparticles, angiogenesis
format article
author Roma-Rodrigues C
Fernandes AR
Baptista PV
author_facet Roma-Rodrigues C
Fernandes AR
Baptista PV
author_sort Roma-Rodrigues C
title Counteracting the effect of leukemia exosomes by antiangiogenic gold nanoparticles
title_short Counteracting the effect of leukemia exosomes by antiangiogenic gold nanoparticles
title_full Counteracting the effect of leukemia exosomes by antiangiogenic gold nanoparticles
title_fullStr Counteracting the effect of leukemia exosomes by antiangiogenic gold nanoparticles
title_full_unstemmed Counteracting the effect of leukemia exosomes by antiangiogenic gold nanoparticles
title_sort counteracting the effect of leukemia exosomes by antiangiogenic gold nanoparticles
publisher Dove Medical Press
publishDate 2019
url https://doaj.org/article/6c1e8356c1824deab5145fc9f5c1203a
work_keys_str_mv AT romarodriguesc counteractingtheeffectofleukemiaexosomesbyantiangiogenicgoldnanoparticles
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