Counteracting the effect of leukemia exosomes by antiangiogenic gold nanoparticles

Int J Nanomedicine. 2019 Aug 26;14:6843-6854. doi: 10.2147/IJN.S215711. eCollection 2019.

Abstract

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: angiogenesis; chorioallantoic membrane; chronic myeloid leukemia; exosomes; gold nanoparticles.

MeSH terms

  • Angiogenesis Inhibitors / chemistry
  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Chick Embryo
  • Chorioallantoic Membrane / drug effects
  • Exosomes / metabolism
  • Exosomes / pathology*
  • Gold / chemistry
  • Gold / pharmacology*
  • Humans
  • Interleukin-8 / metabolism
  • K562 Cells / metabolism
  • Metal Nanoparticles / chemistry
  • Metal Nanoparticles / therapeutic use*
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / metabolism
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factor Receptor-1 / metabolism

Substances

  • Angiogenesis Inhibitors
  • CXCL8 protein, human
  • Interleukin-8
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Gold
  • FLT1 protein, human
  • Vascular Endothelial Growth Factor Receptor-1