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Effectively suppressed angiogenesis-mediated retinoblastoma growth using celastrol nanomicelles

Zhanrong Li1, Zhihua Guo1, Dandan Chu1

  • 1Henan Eye Hospital, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, P. R. China.

Drug Delivery
|February 25, 2020
PubMed

Insights

Celastrol nanomicelles effectively inhibited retinoblastoma growth by targeting the hypoxia-induced HIF-1α/VEGF pathway, thereby reducing tumor angiogenesis. This study highlights a potential therapeutic strategy for retinoblastoma.

Area of Science:

  • Oncology
  • Nanomedicine
  • Molecular Biology

Background:

  • Celastrol, a natural compound, shows anti-retinoblastoma activity, but its mechanism and delivery are unclear.
  • Angiogenesis is crucial for tumor growth and metastasis in retinoblastoma.
  • Developing effective drug delivery systems is essential for improving celastrol's therapeutic potential.

Purpose of the Study:

  • To investigate the anti-angiogenic effects of celastrol on retinoblastoma growth.
  • To elucidate the molecular mechanism underlying celastrol's action, focusing on the HIF-1α/VEGF pathway.
  • To develop and evaluate celastrol-loaded polymeric nanomicelles (CNMs) for improved delivery and efficacy.

Main Methods:

  • Celastrol-loaded polymeric nanomicelles (CNMs) were synthesized to enhance celastrol's solubility.
  • In vivo studies involved xenografted mice treated with CNMs to assess tumor growth and angiogenesis.
  • In vitro assays used human umbilical vascular endothelial cells (EA.hy 926) and chick embryo chorioallantoic membrane to evaluate anti-angiogenic properties and molecular signaling.

Main Results:

  • CNMs significantly reduced tumor weight and volume in retinoblastoma xenografts.
  • CNMs inhibited hypoxia-induced proliferation, migration, and invasion of endothelial cells.
  • CNMs suppressed the hypoxia-induced HIF-1α (hypoxia-inducible factor 1-alpha) and VEGF (vascular endothelial growth factor) signaling pathways.

Conclusions:

  • Celastrol nanomicelles effectively inhibit retinoblastoma growth and angiogenesis.
  • The mechanism involves targeting the HIF-1α/VEGF pathway, crucial for tumor vascularization.
  • CNMs represent a promising nanomedicine approach for retinoblastoma treatment.
Keywords:
CelastrolSO-Rb 50 cellsangiogenesisnanomicellesretinoblastoma

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