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Open AccessArticle

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

1
1601 Parkveiw Ave, Regenerative Medicine and Disability Research Lab, Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford, Rockford, IL 61107, USA
2
Department of Biomedical Sciences, Northwestern University, Evanston, IL 60208, USA
3
Department of Ophthalmology and Visual Sciences, University of Illinois Chicago, Chicago, IL 60612, USA
*
Author to whom correspondence should be addressed.
Nanomaterials 2020, 10(3), 581; https://doi.org/10.3390/nano10030581 (registering DOI)
Received: 28 February 2020 / Revised: 18 March 2020 / Accepted: 19 March 2020 / Published: 22 March 2020
(This article belongs to the Special Issue Nanopharmaceutics)
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. View Full-Text
Keywords: Micelles; PEG-b-PPS; anti-angiogenic; integrin; VEGF Micelles; PEG-b-PPS; anti-angiogenic; integrin; VEGF
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Nagaraj, R.; Stack, T.; Yi, S.; Mathew, B.; Shull, K.R.; Scott, E.A.; Mathew, M.T.; Bijukumar, D.R. High Density Display of an Anti-Angiogenic Peptide on Micelle Surfaces Enhances Their Inhibition of αvβ3 Integrin-Mediated Neovascularization In Vitro. Nanomaterials 2020, 10, 581.

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