In vitro assessment of varying peptide surface density on the suppression of angiogenesis by micelles displaying αvβ3 blocking peptides

Neha Phani Bhushan; Trevor Stack; Evan A. Scott; Kenneth R. Shull; Benjamin Mathew; Divya Bijukumar

doi:10.1002/jbm.b.35154

In vitro assessment of varying peptide surface density on the suppression of angiogenesis by micelles displaying αvβ3 blocking peptides

Neha Phani Bhushan, Trevor Stack, Evan A. Scott, Kenneth R. Shull, Benjamin Mathew, Divya Bijukumar^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

Ligand targeted therapy (LTT) is a precision medicine strategy that can selectively target diseased cells while minimizing off-target effects on healthy cells. Integrin-targeted LTT has been developed recently for angiogenesis-related diseases. However, the clinical success is based on the optimal design of the nanoparticles for inducing receptor clustering within the cell membrane. The current study focused on determining the surface density of Ser-Asp-Val containing anti-integrin heptapeptide on poly (ethylene glycol)-b-poly(propylene sulfide) micelles (MC) required for anti-angiogenic effects on HUVECs. Varying peptide density on PEG-b-PPS/Pep-PA MCs (Pep-PA-Peptide-palmitoleic acid) was used in comparison to a random peptide (SGV) and cRGD (cyclic-Arginine-Glycine-Aspartic acid) construct at 5%-density on MCs. Immunocytochemistry using CD51/CD31 antibody was performed to study the integrin blocking by MCs. In addition, the expression of VWF and PECAM-1, cell migration and tube formation was evaluated in the presence of PEG-b-PPS/Pep-PA MCs. The results show PEG-b-PPS/SDV-PA MCs with 5%-peptide density to achieve significantly higher αvβ3 blocking compared to random peptide as well as cRGD. In addition, αvβ3 blocking via MCs further reduced the expression of vWF and PECAM-1 angiogenesis protein expression in HUVECs. Although a significant level of integrin blocking was observed for 1%-peptide density on MCs, the cell migration and tube formation were not significantly affected. In conclusion, the results of this study demonstrate that the peptide surface density on PEG-b-PPS/Pep-PA MCs has a significant impact in integrin blocking as well as inhibiting angiogenesis during LTT. The outcomes of this study provides insight into the design of ligand targeted nanocarriers for various disease conditions.

Original language	English (US)
Pages (from-to)	343-353
Number of pages	11
Journal	Journal of Biomedical Materials Research - Part B Applied Biomaterials
Volume	111
Issue number	2
DOIs	https://doi.org/10.1002/jbm.b.35154
State	Published - Feb 2023

Funding

The authors acknowledge the support from Regenerative Medicine and Disability Lab at Biomedical Sciences. The authors also thank the support from NUANCE/SHyNE facilities at Northwestern University for CryoTEM analysis. The authors acknowledge the financial support by NIH/NIBIB R03EB032602, Blazer foundation, and Medical Biotechnology Program at Biomedical Sciences, UIC Rockford. The authors than thank Dr. Fanfan Du, Biomedical Engineering, Northwestern University for helping with polymer synthesis.

Keywords

LTT
PEG-b-PPS
anti-angiogenic peptide
micelles
αvβ3

ASJC Scopus subject areas

Biomaterials
Biomedical Engineering

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/jbm.b.35154

Cite this

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title = "In vitro assessment of varying peptide surface density on the suppression of angiogenesis by micelles displaying αvβ3 blocking peptides",

abstract = "Ligand targeted therapy (LTT) is a precision medicine strategy that can selectively target diseased cells while minimizing off-target effects on healthy cells. Integrin-targeted LTT has been developed recently for angiogenesis-related diseases. However, the clinical success is based on the optimal design of the nanoparticles for inducing receptor clustering within the cell membrane. The current study focused on determining the surface density of Ser-Asp-Val containing anti-integrin heptapeptide on poly (ethylene glycol)-b-poly(propylene sulfide) micelles (MC) required for anti-angiogenic effects on HUVECs. Varying peptide density on PEG-b-PPS/Pep-PA MCs (Pep-PA-Peptide-palmitoleic acid) was used in comparison to a random peptide (SGV) and cRGD (cyclic-Arginine-Glycine-Aspartic acid) construct at 5%-density on MCs. Immunocytochemistry using CD51/CD31 antibody was performed to study the integrin blocking by MCs. In addition, the expression of VWF and PECAM-1, cell migration and tube formation was evaluated in the presence of PEG-b-PPS/Pep-PA MCs. The results show PEG-b-PPS/SDV-PA MCs with 5%-peptide density to achieve significantly higher αvβ3 blocking compared to random peptide as well as cRGD. In addition, αvβ3 blocking via MCs further reduced the expression of vWF and PECAM-1 angiogenesis protein expression in HUVECs. Although a significant level of integrin blocking was observed for 1%-peptide density on MCs, the cell migration and tube formation were not significantly affected. In conclusion, the results of this study demonstrate that the peptide surface density on PEG-b-PPS/Pep-PA MCs has a significant impact in integrin blocking as well as inhibiting angiogenesis during LTT. The outcomes of this study provides insight into the design of ligand targeted nanocarriers for various disease conditions.",

keywords = "LTT, PEG-b-PPS, anti-angiogenic peptide, micelles, αvβ3",

author = "Bhushan, {Neha Phani} and Trevor Stack and Scott, {Evan A.} and Shull, {Kenneth R.} and Benjamin Mathew and Divya Bijukumar",

note = "Publisher Copyright: {\textcopyright} 2022 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials published by Wiley Periodicals LLC.",

year = "2023",

month = feb,

doi = "10.1002/jbm.b.35154",

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volume = "111",

pages = "343--353",

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In vitro assessment of varying peptide surface density on the suppression of angiogenesis by micelles displaying αvβ3 blocking peptides. / Bhushan, Neha Phani; Stack, Trevor; Scott, Evan A. et al.
In: Journal of Biomedical Materials Research - Part B Applied Biomaterials, Vol. 111, No. 2, 02.2023, p. 343-353.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - In vitro assessment of varying peptide surface density on the suppression of angiogenesis by micelles displaying αvβ3 blocking peptides

AU - Bhushan, Neha Phani

AU - Stack, Trevor

AU - Scott, Evan A.

AU - Shull, Kenneth R.

AU - Mathew, Benjamin

AU - Bijukumar, Divya

PY - 2023/2

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N2 - Ligand targeted therapy (LTT) is a precision medicine strategy that can selectively target diseased cells while minimizing off-target effects on healthy cells. Integrin-targeted LTT has been developed recently for angiogenesis-related diseases. However, the clinical success is based on the optimal design of the nanoparticles for inducing receptor clustering within the cell membrane. The current study focused on determining the surface density of Ser-Asp-Val containing anti-integrin heptapeptide on poly (ethylene glycol)-b-poly(propylene sulfide) micelles (MC) required for anti-angiogenic effects on HUVECs. Varying peptide density on PEG-b-PPS/Pep-PA MCs (Pep-PA-Peptide-palmitoleic acid) was used in comparison to a random peptide (SGV) and cRGD (cyclic-Arginine-Glycine-Aspartic acid) construct at 5%-density on MCs. Immunocytochemistry using CD51/CD31 antibody was performed to study the integrin blocking by MCs. In addition, the expression of VWF and PECAM-1, cell migration and tube formation was evaluated in the presence of PEG-b-PPS/Pep-PA MCs. The results show PEG-b-PPS/SDV-PA MCs with 5%-peptide density to achieve significantly higher αvβ3 blocking compared to random peptide as well as cRGD. In addition, αvβ3 blocking via MCs further reduced the expression of vWF and PECAM-1 angiogenesis protein expression in HUVECs. Although a significant level of integrin blocking was observed for 1%-peptide density on MCs, the cell migration and tube formation were not significantly affected. In conclusion, the results of this study demonstrate that the peptide surface density on PEG-b-PPS/Pep-PA MCs has a significant impact in integrin blocking as well as inhibiting angiogenesis during LTT. The outcomes of this study provides insight into the design of ligand targeted nanocarriers for various disease conditions.

AB - Ligand targeted therapy (LTT) is a precision medicine strategy that can selectively target diseased cells while minimizing off-target effects on healthy cells. Integrin-targeted LTT has been developed recently for angiogenesis-related diseases. However, the clinical success is based on the optimal design of the nanoparticles for inducing receptor clustering within the cell membrane. The current study focused on determining the surface density of Ser-Asp-Val containing anti-integrin heptapeptide on poly (ethylene glycol)-b-poly(propylene sulfide) micelles (MC) required for anti-angiogenic effects on HUVECs. Varying peptide density on PEG-b-PPS/Pep-PA MCs (Pep-PA-Peptide-palmitoleic acid) was used in comparison to a random peptide (SGV) and cRGD (cyclic-Arginine-Glycine-Aspartic acid) construct at 5%-density on MCs. Immunocytochemistry using CD51/CD31 antibody was performed to study the integrin blocking by MCs. In addition, the expression of VWF and PECAM-1, cell migration and tube formation was evaluated in the presence of PEG-b-PPS/Pep-PA MCs. The results show PEG-b-PPS/SDV-PA MCs with 5%-peptide density to achieve significantly higher αvβ3 blocking compared to random peptide as well as cRGD. In addition, αvβ3 blocking via MCs further reduced the expression of vWF and PECAM-1 angiogenesis protein expression in HUVECs. Although a significant level of integrin blocking was observed for 1%-peptide density on MCs, the cell migration and tube formation were not significantly affected. In conclusion, the results of this study demonstrate that the peptide surface density on PEG-b-PPS/Pep-PA MCs has a significant impact in integrin blocking as well as inhibiting angiogenesis during LTT. The outcomes of this study provides insight into the design of ligand targeted nanocarriers for various disease conditions.

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KW - anti-angiogenic peptide

KW - micelles

KW - αvβ3

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In vitro assessment of varying peptide surface density on the suppression of angiogenesis by micelles displaying αvβ3 blocking peptides

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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