Delivery of sodium morrhuate to hemangioma endothelial cells using immunoliposomes conjugated with anti-VEGFR2/KDR antibody

Int J Nanomedicine. 2017 Sep 19:12:6963-6972. doi: 10.2147/IJN.S144056. eCollection 2017.

Abstract

Hemangioma is a common benign tumor affecting infants. In this study, we prepared sodium morrhuate immunoliposomes through encapsulation of sodium morrhuate with liposomes coupled with an anti-VEGFR2/KDR antibody and examined its effect on the biology of human hemangioma endothelial cells (HECs). It was found that compared to the liposomal sodium morrhuate group, treatment with sodium morrhuate immunoliposomes facilitated cell detachment and apoptotic death. Confocal microscopy analysis revealed that sodium morrhuate immunoliposomes had a higher binding activity to HECs than liposomal sodium morrhuate. Apoptosis analysis further demonstrated that treatment with liposomal sodium morrhuate or sodium morrhuate immunoliposomes significantly induced apoptosis in HECs, compared to the control group. Western blot analysis revealed an induction of caspase-3 and caspase-9 levels and reduction of caspase-8 and Bcl-2 levels in HECs treated with liposomal sodium morrhuate or sodium morrhuate immunoliposomes. Taken together, these results indicate that sodium morrhuate immunoliposomes have an increased capacity to target HECs and promote mitochondrial apoptosis. Therefore, sodium morrhuate immunoliposomes may represent a promising agent in the treatment of hemangiomas.

Keywords: KDR; VEGF2; apoptosis; hemangioma; liposome.

MeSH terms

  • Antibodies, Monoclonal / administration & dosage*
  • Biological Assay
  • Cell Death / drug effects
  • Cell Shape / drug effects
  • Endothelial Cells / drug effects
  • Endothelial Cells / pathology*
  • Endothelial Cells / ultrastructure
  • Hemangioma / drug therapy*
  • Humans
  • Liposomes / administration & dosage
  • Sodium Morrhuate / administration & dosage*
  • Sodium Morrhuate / pharmacology
  • Sodium Morrhuate / therapeutic use*
  • Vascular Endothelial Growth Factor Receptor-2 / immunology*

Substances

  • Antibodies, Monoclonal
  • Liposomes
  • Sodium Morrhuate
  • KDR protein, human
  • Vascular Endothelial Growth Factor Receptor-2