E-Selectin Targeted Gold Nanoshells to Inhibit Breast Cancer Cell Binding to Lung Endothelial Cells
Year: 2023
Type: article
Abstract: 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.
Source: ACS Applied Nano Materials
Authors: Z. Fereshteh, M.N. Dang, C. Wenck, E.S. Day, J.H. Slater
Institution: University of Delaware
Language: English
Field: Materials Science
Domain: Physical Sciences
Open Access status: green
Awards: G3052557138, G3115553707, Multifunctional siRNA/antibody nanocarriers to treat metastatic triple-negative breast cancer, Delaware EPSCoR: Meeting Delaware's 21st Century Water and Energy Challenges through Research, Education, and Innovation, Maximizing the delivery and efficacy of miRNA therapeutics through nanocarrier design, G6472626693, CAREER: Development of a Tissue-Engineered Model of Ischemic Microstroke, Delaware INBRE, Center of Biomedical Research Excellence in Cardiovascular Health, Chemistry-Biology Interface Predoctoral Training Grant 2024-2029
OpenAlex ID: W4313894086