Abstract

Previously, we noted that carboxylated multi-walled carbon nanotubes (cMWNTs) coated with Pluronic® F-108 (PF108) bound to and were accumulated by macrophages, but that pristine multi-walled carbon nanotubes (pMWNTs) coated with PF108 were not (Wang et al., Nanotoxicology 2018, 12, 677). Subsequent studies with Chinese hamster ovary (CHO) cells that overexpressed scavenger receptor A1 (SR-A1) and with macrophages derived from mice knocked out for SR-A1 provided evidence that SR-A1 was a receptor of PF108-cMWNTs (Wang et al., Nanomaterials (Basel) 2020, 10, 2417). Herein, we replaced the PF108 coat with bovine serum albumin (BSA) to investigate how a BSA corona affected the interaction of multi-walled carbon nanotubes (MWNTs) with cells. Both BSA-coated cMWNTs and pMWNTs bound to and were accumulated by RAW 264.7 macrophages, although the cells bound two times more BSA-coated cMWNT than pMWNTs. RAW 264.7 cells that were deleted for SR-A1 using CRISPR-Cas9 technology had markedly reduced binding and accumulation of both BSA-coated cMWNTs and pMWNTs, suggesting that SR-A1 was responsible for the uptake of both MWNT types. Moreover, CHO cells that ectopically expressed SR-A1 accumulated both MWNT types, whereas wild-type CHO cells did not. One model to explain these results is that SR-A1 can interact with two structural features of BSA-coated cMWNTs, one inherent to the oxidized nanotubes (such as COOH and other oxidized groups) and the other provided by the BSA corona; whereas SR-A1 only interacts with the BSA corona of BSA-pMWNTs.

Highlights

  • Pluronic® F-108 (PF108)-coated pristine multiwalled carbon nanotubes (pMWNTs) fail to bind to macrophages but BSAcoated pMWNTs do bind, suggesting that a bovine serum albumin (BSA) corona confers the ability of pMWNTs to bind to cells

  • In this article we studied the interaction of BSA-multi-walled carbon nanotubes (MWNTs) with macrophages using a direct binding assay under highly controlled conditions where the influence of nanotube functionalization and protein coronas could be controlled

  • The results demonstrated that the binding of both BSA-carboxylated MWNTs (cMWNTs) and BSA-pMWNTs to the cell surface was a dose-dependent and saturable function of the applied MWNT concentration

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Summary

Introduction

The interaction of engineered nanoparticles (ENPs) with cells is influenced by a corona of macromolecules that deposit on the ENP surface from the surrounding biological fluid. Corona components may provide dominant features controlling the interaction of ENPs with specific cell surface binding sites, often followed by ENP internalization and a subsequent response by the cells. Understanding what corona components are present on an ENP and how they interface with cells is important to provide rational approaches for promoting positive responses, such as targeted drug delivery, or mitigating negative responses, such as toxicity. Understanding ENP coronas is challenging because the potential corona components in complex biological environments are diverse and the properties of ENP surfaces vary widely.

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