4.8 Article

Cell surface biotinylation to identify the receptors involved in nanoparticle uptake into endothelial cells

Journal

ACTA BIOMATERIALIA
Volume 155, Issue -, Pages 507-520

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.actbio.2022.11.010

Keywords

Targeted drug delivery; Reversible biotinylation; Protein corona; Cellular receptors; Endothelial cells

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Targeted drug delivery relies on the specific interaction between nanocarriers and cell surface receptors for efficient internalization. By using cell surface biotinylation, we identified the receptors mediating nanoparticle uptake. Vitronectin corona was found to enhance the uptake of nanoparticles in brain and liver endothelial cells by targeting integrin receptors.
Targeted drug delivery requires -among others-specific interaction of nanocarriers with cell surface re-ceptors enabling efficient internalization into the targeted cells. Thus, identification of receptors allow-ing efficient nanocarrier uptake is essential to improve the design of targeted nanomedicines. Here we used methods based on cell surface biotinylation to identify cell surface receptors mediating nanopar-ticle uptake by cells. We used human brain and liver endothelial cells as representative examples of cells typically showing very low and very high nanoparticle uptake, respectively. Amino-modified and carboxylated silica were used as model nanoparticles usually associated with high and low uptake into cells, respectively, and carrying different coronas after exposure in full human plasma. Using cell sur-face biotinylation of live cells and receptor pull-down assays, we compared the receptors internalized in control untreated cells and those internalized upon exposure to nanoparticles. In this way, we identified receptors associated with (high) nanoparticle uptake. The candidate receptors were further validated by decorating the nanoparticles with an artificial corona consisting of the respective receptor ligands. We found that a vitronectin corona can be used to target integrin receptors and strongly enhances nanopar-ticle uptake in brain and liver endothelial cells. The increased uptake was maintained in the presence of serum, suggesting that the vitronectin-corona could resist interaction and competition with serum. Fur-thermore, plasminogen-coated nanoparticles promoted uptake in endothelial cells of the liver, but not of the brain. The presented approach using reversible biotinylation of cell surface receptors in live cells al-lows for receptor-based targeting of nanocarriers that are instrumental in nanoparticle uptake, which can be exploited for targeted drug delivery.

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