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

Simple item page
Author(s)Fereshteh, Z.
Author(s)Dang, M. N.
Author(s)Wenck, C.
Author(s)Day, E. S.
Author(s)Slater, J. H.
Date Accessioned2023-03-21T18:38:15Z
Date Available2023-03-21T18:38:15Z
Publication Date2023-01-27
DescriptionThis 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
AbstractExtravasation 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.
SponsorThis work was supported by the National Institutes of Health (NIH) under grant numbers R01CA211925 (ESD), R35GM119659 (ESD), T32GM133395 (MND), and P20GM113125 (JHS) and the National Science Foundation 1751797 (JHS). Microscopy access was supported by grants from the NIH (P20GM103446), the National Science Foundation (IIA-1301765), and the State of Delaware. The content is solely the responsibility of the authors and does not necessarily reflect the views of the funding agencies.
CitationFereshteh, 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
ISSN2574-0970
URLhttps://udspace.udel.edu/handle/19716/32545
Languageen_US
PublisherACS Applied Nano Material
Keywordscirculating tumor cells
Keywordsmetastasis
Keywordsnanomedicine
Keywordsextravasation
Keywordsnanoparticles
Keywordstargeted therapy
TitleE-Selectin Targeted Gold Nanoshells to Inhibit Breast Cancer Cell Binding to Lung Endothelial Cells
TypeArticle
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
E-Selection Targeted Gold Nanoshells.pdf
Size:
2.24 MB
Format:
Adobe Portable Document Format
Description:
Main article
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
2.22 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Open Access Publications