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Counteracting the effect of leukemia exosomes by antiangiogenic gold nanoparticles

Authors Roma-Rodrigues C, Fernandes AR, Baptista PV

Received 14 May 2019

Accepted for publication 19 July 2019

Published 26 August 2019 Volume 2019:14 Pages 6843—6854

DOI https://doi.org/10.2147/IJN.S215711

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Thomas J. Webster


Catarina Roma-Rodrigues, Alexandra R Fernandes, Pedro V Baptista

UCIBIO, Departamento de Ciências da Vida, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, Campus de Caparica, Caparica 2829-516, Portugal

Correspondence: Alexandra R Fernandes; Pedro V Baptista
UCIBIO, Departamento de Ciências da Vida, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, Campus de Caparica, Caparica 2829-516, Portugal
Tel +351 21 294 8530
Fax +351 21 294 8530
Email ma.fernandes@fct.unl.pt
pmvb@fct.unl.pt

Purpose: 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

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