High density display of an anti-angiogenic peptide on micelle surfaces enhances their inhibition of αvβ3 integrin-mediated neovascularization in vitro

Rajini Nagaraj, Trevor Stack, Sijia Yi, Benjamin Mathew, Kenneth R. Shull, Evan A. Scott, Mathew T. Mathew, Divya Rani Bijukumar*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Diabetic retinopathy (DR), Retinopathy of Pre-maturity (ROP), and Age-related Macular Degeneration (AMD) are multifactorial manifestations associated with abnormal growth of blood vessels in the retina. These three diseases account for 5% of the total blindness and vision impairment in the US alone. The current treatment options involve heavily invasive techniques such as frequent intravitreal administration of anti-VEGF (vascular endothelial growth factor) antibodies, which pose serious risks of endophthalmitis, retinal detachment and a multitude of adverse effects stemming from the diverse physiological processes that involve VEGF. To overcome these limitations, this current study utilizes a micellar delivery vehicle (MC) decorated with an anti-angiogenic peptide (aANGP) that inhibits αvβ3 mediated neovascularization using primary endothelial cells (HUVEC). Stable incorporation of the peptide into the micelles (aANGP-MCs) for high valency surface display was achieved with a lipidated peptide construct. After 24 h of treatment, aANGP-MCs showed significantly higher inhibition of proliferation and migration compared to free from aANGP peptide. A tube formation assay clearly demonstrated a dose-dependent angiogenic inhibitory effect of aANGP-MCs with a maximum inhibition at 4 μg/mL, a 1000-fold lower concentration than that required for free from aANGP to display a biological effect. These results demonstrate valency-dependent enhancement in the therapeutic efficacy of a bioactive peptide following conjugation to nanoparticle surfaces and present a possible treatment alternative to anti-VEGF antibody therapy with decreased side effects and more versatile options for controlled delivery.

Original languageEnglish (US)
Article number581
JournalNanomaterials
Volume10
Issue number3
DOIs
StatePublished - Mar 2020

Keywords

  • Anti-angiogenic
  • Integrin
  • Micelles
  • PEG-b-PPS
  • VEGF

ASJC Scopus subject areas

  • Chemical Engineering(all)
  • Materials Science(all)

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