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

• Published in: Nanomaterials (Basel, Switzerland) Vol. 10; no. 3; p. 581
• Main Authors: Nagaraj, Rajini, Stack, Trevor, Yi, Sijia, Mathew, Benjamin, Shull, Kenneth R, Scott, Evan A, Mathew, Mathew T, Bijukumar, Divya Rani
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 22.03.2020; MDPI
• Subjects: Age; Age related diseases; Angiogenesis; anti-angiogenic; Antiangiogenics; Antibodies; Biological effects; Blindness; Blood vessels; Chromatography; Conjugation; Diabetes mellitus; Diabetic retinopathy; Endophthalmitis; Endothelial cells; Eye diseases; Growth factors; Hemorrhage; Hypoxia; Immunotherapy; integrin; Lipids; Macular degeneration; Mass spectrometry; Micelles; Nanoparticles; peg-b-pps; Peptides; Physiological effects; Polymers; Retina; Retinopathy; Scientific imaging; Side effects; Valency; Vascular endothelial growth factor; Vascularization; vegf; St Louis Missouri; United States > US; anti-angiogenic; integrin; Micelles; VEGF; PEG-b-PPS
• ISSN: 2079-4991; 2079-4991
• DOI: 10.3390/nano10030581

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.