High Density Display of an Anti-Angiogenic Peptide on Micelle Surfaces Enhances Their Inhibition of αvβ3 Integrin-Mediated Neovascularization In Vitro.
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| Title: | High Density Display of an Anti-Angiogenic Peptide on Micelle Surfaces Enhances Their Inhibition of αvβ3 Integrin-Mediated Neovascularization In Vitro. |
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| Authors: | Nagaraj, Rajini1 (AUTHOR) rnagar5@uic.edu, Stack, Trevor2 (AUTHOR) trevorstack2019@u.northwestern.edu, Yi, Sijia2 (AUTHOR) sijia.yi@northwestern.edu, Mathew, Benjamin3 (AUTHOR) bmathew3@uic.edu, Shull, Kenneth R2 (AUTHOR) k-shull@northwestern.edu, Scott, Evan A2 (AUTHOR) evan.scott@northwestern.edu, Mathew, Mathew T1 (AUTHOR) mtmathew@uic.edu, Bijukumar, Divya Rani1 (AUTHOR) drbiju2@uic.edu |
| Source: | Nanomaterials (2079-4991). Mar2020, Vol. 10 Issue 3, p581. 1p. |
| Subjects: | Retrolental fibroplasia, Neovascularization, Vascular endothelial growth factors, Vascular endothelial growth factor antagonists, Treatment effectiveness, Micelles, Diabetic retinopathy, Retinal detachment |
| 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. [ABSTRACT FROM AUTHOR] |
| Copyright of Nanomaterials (2079-4991) is the property of MDPI and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
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| Header | DbId: egs DbLabel: Engineering Source An: 142524888 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: High Density Display of an Anti-Angiogenic Peptide on Micelle Surfaces Enhances Their Inhibition of αvβ3 Integrin-Mediated Neovascularization In Vitro. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Nagaraj%2C+Rajini%22">Nagaraj, Rajini</searchLink><relatesTo>1</relatesTo> (AUTHOR)<i> rnagar5@uic.edu</i><br /><searchLink fieldCode="AR" term="%22Stack%2C+Trevor%22">Stack, Trevor</searchLink><relatesTo>2</relatesTo> (AUTHOR)<i> trevorstack2019@u.northwestern.edu</i><br /><searchLink fieldCode="AR" term="%22Yi%2C+Sijia%22">Yi, Sijia</searchLink><relatesTo>2</relatesTo> (AUTHOR)<i> sijia.yi@northwestern.edu</i><br /><searchLink fieldCode="AR" term="%22Mathew%2C+Benjamin%22">Mathew, Benjamin</searchLink><relatesTo>3</relatesTo> (AUTHOR)<i> bmathew3@uic.edu</i><br /><searchLink fieldCode="AR" term="%22Shull%2C+Kenneth+R%22">Shull, Kenneth R</searchLink><relatesTo>2</relatesTo> (AUTHOR)<i> k-shull@northwestern.edu</i><br /><searchLink fieldCode="AR" term="%22Scott%2C+Evan+A%22">Scott, Evan A</searchLink><relatesTo>2</relatesTo> (AUTHOR)<i> evan.scott@northwestern.edu</i><br /><searchLink fieldCode="AR" term="%22Mathew%2C+Mathew+T%22">Mathew, Mathew T</searchLink><relatesTo>1</relatesTo> (AUTHOR)<i> mtmathew@uic.edu</i><br /><searchLink fieldCode="AR" term="%22Bijukumar%2C+Divya+Rani%22">Bijukumar, Divya Rani</searchLink><relatesTo>1</relatesTo> (AUTHOR)<i> drbiju2@uic.edu</i> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Nanomaterials+%282079-4991%29%22">Nanomaterials (2079-4991)</searchLink>. Mar2020, Vol. 10 Issue 3, p581. 1p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Retrolental+fibroplasia%22">Retrolental fibroplasia</searchLink><br /><searchLink fieldCode="DE" term="%22Neovascularization%22">Neovascularization</searchLink><br /><searchLink fieldCode="DE" term="%22Vascular+endothelial+growth+factors%22">Vascular endothelial growth factors</searchLink><br /><searchLink fieldCode="DE" term="%22Vascular+endothelial+growth+factor+antagonists%22">Vascular endothelial growth factor antagonists</searchLink><br /><searchLink fieldCode="DE" term="%22Treatment+effectiveness%22">Treatment effectiveness</searchLink><br /><searchLink fieldCode="DE" term="%22Micelles%22">Micelles</searchLink><br /><searchLink fieldCode="DE" term="%22Diabetic+retinopathy%22">Diabetic retinopathy</searchLink><br /><searchLink fieldCode="DE" term="%22Retinal+detachment%22">Retinal detachment</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: 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. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Nanomaterials (2079-4991) is the property of MDPI and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.3390/nano10030581 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 1 StartPage: 581 Subjects: – SubjectFull: Retrolental fibroplasia Type: general – SubjectFull: Neovascularization Type: general – SubjectFull: Vascular endothelial growth factors Type: general – SubjectFull: Vascular endothelial growth factor antagonists Type: general – SubjectFull: Treatment effectiveness Type: general – SubjectFull: Micelles Type: general – SubjectFull: Diabetic retinopathy Type: general – SubjectFull: Retinal detachment Type: general Titles: – TitleFull: High Density Display of an Anti-Angiogenic Peptide on Micelle Surfaces Enhances Their Inhibition of αvβ3 Integrin-Mediated Neovascularization In Vitro. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Nagaraj, Rajini – PersonEntity: Name: NameFull: Stack, Trevor – PersonEntity: Name: NameFull: Yi, Sijia – PersonEntity: Name: NameFull: Mathew, Benjamin – PersonEntity: Name: NameFull: Shull, Kenneth R – PersonEntity: Name: NameFull: Scott, Evan A – PersonEntity: Name: NameFull: Mathew, Mathew T – PersonEntity: Name: NameFull: Bijukumar, Divya Rani IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 03 Text: Mar2020 Type: published Y: 2020 Identifiers: – Type: issn-print Value: 20794991 Numbering: – Type: volume Value: 10 – Type: issue Value: 3 Titles: – TitleFull: Nanomaterials (2079-4991) Type: main |
| ResultId | 1 |
