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  • High Density Display of an Anti-Angiogenic Peptide on Micelle Surfaces Enhances Their Inhibition of αvβ3 Integrin-Mediated Neovascularization In Vitro.

High Density Display of an Anti-Angiogenic Peptide on Micelle Surfaces Enhances Their Inhibition of αvβ3 Integrin-Mediated Neovascularization In Vitro.

Nanomaterials (Basel, Switzerland) (2020-04-03)
Rajini Nagaraj, Trevor Stack, Sijia Yi, Benjamin Mathew, Kenneth R Shull, Evan A Scott, Mathew T Mathew, Divya Rani Bijukumar
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.

MATERIALS
Product Number
Brand
Product Description

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Thiosalicylic acid, 97%
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Dichloromethane, anhydrous, ≥99.8%, contains 40-150 ppm amylene as stabilizer
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Endothelial Cell Growth Medium (500 ml)
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Trifluoroacetic acid, ReagentPlus®, 99%
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Hydrochloric acid, 36.5-38.0%, BioReagent, for molecular biology
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ECM Gel from Engelbreth-Holm-Swarm murine sarcoma, liquid, BioReagent, suitable for cell culture
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1-Methyl-2-pyrrolidinone, anhydrous, 99.5%
SAFC
Collagen Coating Solution (50 ML)
Sephadex® LH-20, Cytiva 17-0090-02, pack of 500 g
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Human Umbilical Vein Endothelial Cells: HUVEC: Pre-Screened for Angiogenesis & VEGF signaling, neonatal