E-Selectin Targeted Gold Nanoshells to Inhibit Breast Cancer Cell Binding to Lung Endothelial Cells

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Biology

Background:

• Cancer metastasis involves circulating tumor cells (CTCs) extravasating from vasculature.
• CTCs adhere to endothelial cell adhesion molecules (CAMs) on endothelial cells (ECs) for flow arrest.
• E-selectin is a key CAM implicated in CTC binding.

Purpose of the Study:

• To investigate the efficacy of antibody-functionalized gold nanoshells in blocking E-selectin.
• To inhibit the binding of cancer cells to human lung microvascular endothelial cells (HMVEC-Ls).
• To understand how synthesis parameters affect antibody-functionalized nanoshell properties and function.

Main Methods:

• Synthesized antibody-functionalized gold nanoshells using directional and non-directional conjugation techniques.
• Varied synthesis parameters including linker length, passivating agents, and antibody ratio.
• Quantified nanoshell binding to HMVEC-Ls under non-inflamed and TNF-α-inflamed conditions.
• Assessed the inhibition of MDA-MB-231 (triple-negative breast cancer) cell binding to HMVEC-Ls.

Main Results:

• Non-directional conjugation yielded higher antibody loading on nanoshells compared to directional conjugation.
• Both conjugation methods resulted in similar nanoshell binding to HMVEC-Ls at equivalent antibody concentrations.
• E-selectin-targeted nanoshells reduced MDA-MB-231 cell binding to HMVEC-Ls by up to 41% in vitro.
• Characterized nanoshells by hydrodynamic diameter, zeta potential, and antibody loading density.

Conclusions:

• Antibody-functionalized gold nanoshells can be synthesized with tunable properties.
• These nanoshells effectively inhibit CTC binding to endothelial cells by targeting E-selectin.
• This strategy offers a potential therapeutic approach to impede cancer metastasis.