Mechanism of anti-angiogenic property of gold nanoparticles: role of nanoparticle size and surface charge

Arvizo, Rochelle R.; Rana, Subinoy; Miranda, Oscar R.; Bhattacharya, Resham; Rotello, Vincent M.; Mukherjee, Priyabrata

doi:10.1016/j.nano.2011.01.011

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Volume 7, Issue 5 , Pages 580-587, October 2011

Mechanism of anti-angiogenic property of gold nanoparticles: role of nanoparticle size and surface charge

Rochelle R. Arvizo, PhD
- Department of Biochemistry and Molecular Biology, College of Medicine, Mayo Clinic, Rochester, Minnesota
Subinoy Rana, MSc
- Department of Chemistry, University of Massachusetts, Amherst, Massachusetts
Oscar R. Miranda, PhD
- Department of Chemistry, University of Massachusetts, Amherst, Massachusetts
Resham Bhattacharya, PhD
- Department of Biochemistry and Molecular Biology, College of Medicine, Mayo Clinic, Rochester, Minnesota
Vincent M. Rotello, PhD
- Department of Chemistry, University of Massachusetts, Amherst, Massachusetts
Priyabrata Mukherjee, PhD
- Department of Biochemistry and Molecular Biology, College of Medicine, Mayo Clinic, Rochester, Minnesota
- Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, Minnesota
- Mayo Clinic Cancer Center, Mayo Clinic College of Medicine, Rochester, Minnesota
- Corresponding author: Mayo Clinic, Guggenheim 13, 200 1st Street, SW Rochester, MN 55905, USA.

Received 11 October 2010; accepted 16 January 2011. published online 18 February 2011.

Abstract

Discovering therapeutic inorganic nanoparticles (NPs) is evolving as an important area of research in the emerging field of nanomedicine. Recently, we reported the anti-angiogenic property of gold nanoparticles (GNPs): It inhibits the function of pro-angiogenic heparin-binding growth factors (HB-GFs), such as vascular endothelial growth factor 165 (VEGF165) and basic fibroblast growth factor (bFGF), etc. However, the mechanism through which GNPs imparts such an effect remains to be investigated. Using GNPs of different sizes and surface charges, we demonstrate here that a naked GNP surface is required and core size plays an important role to inhibit the function of HB-GFs and subsequent intracellular signaling events. We also demonstrate that the inhibitory effect of GNPs is due to the change in HB-GFs conformation/configuration (denaturation) by the NPs, whereas the conformations of non-HB-GFs remain unaffected. We believe that this significant study will help structure-based design of therapeutic NPs to inhibit the functions of disease-causing proteins.

From the Clinical Editor

In this landmark paper by Arvizo and colleagues, the angiogenesis inhibitor effects of gold nanoparticles were investigated as the function of size and charge. This study will pave the way to the development of therapeutic NPs that inhibit the functions of pathogenic proteins.

Graphical Abstract

Binding of heparin-binding growth factors (HB-GFs) to gold nanoparticles leads to the inhibition of their function due to change in the protein structure.