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

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ACS Applied Nano Material
Extravasation of circulating tumor cells (CTCs) from the vasculature is a key step in cancer metastasis. CTCs bind to cell adhesion molecules (CAMs) expressed by endothelial cells (ECs) for flow arrest prior to extravasation. While a number of EC-expressed CAMs have been implicated in facilitating CTC binding, this work investigated the efficacy of inhibiting cancer cell binding to human lung microvascular ECs via antibody blocking of E-selectin using antibody-functionalized gold nanoshells (NS). The antibody-functionalized gold NS were synthesized using both directional and non-directional antibody conjugation techniques with variations in synthesis parameters (linker length, amount of passivating agents, and ratio of antibodies to NS) to gain a better understanding of these properties on the resultant hydrodynamic diameter, zeta potential, and antibody loading density. We quantified the ability of E-selectin antibody-functionalized NS to bind human lung microvascular endothelial cells (HMVEC-Ls) under non-inflamed and inflamed (TNF-α) conditions to inhibit binding of triple-negative MDA-MB-231s. E-selectin-targeted NS prepared using non-directional conjugation had higher antibody loading than those prepared via directional conjugation, resulting in the conjugates having similar overall binding to HMVEC-Ls at a given antibody concentration. E-selectin-targeted NS reduced MDA-MB-231 binding to HMVEC-Ls by up to 41% as determined using an in vitro binding assay. These results provide useful insights into the characteristics of antibody-functionalized NS prepared under different conditions while also demonstrating proof of concept that these conjugates hold potential to inhibit CTC binding to ECs, a critical step in extravasation during metastasis.
This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Applied Nano Material, copyright © 2023 American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see. https://doi.org/10.1021/acsanm.2c04967. This article will be embargoed until 01/27/2024. The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsanm.2c04967
circulating tumor cells, metastasis, nanomedicine, extravasation, nanoparticles, targeted therapy
Fereshteh, Z., Dang, M. N., Wenck, C., Day, E. S., & Slater, J. H. (2023). E-Selectin Targeted Gold Nanoshells to Inhibit Breast Cancer Cell Binding to Lung Endothelial Cells. ACS Applied Nano Materials, 6(2), 1315–1324. https://doi.org/10.1021/acsanm.2c04967