Adsorbed Proteins Influence the Biological Activity and Molecular Targeting of Nanomaterials

TLDR

Nanomaterial toxic potential is uncertain because specific physicochemical properties act at unique cellular sites, and damaged or altered albumin is rapidly cleared from circulation by scavenger receptors. The study examined how surface‑adsorbed proteins on single‑walled carbon nanotubes and 10‑nm amorphous silica influence uptake or toxicity in RAW 264.7 macrophage‑like cells. The authors compared protein adsorption profiles on SWCNTs and amorphous silica, measured Cox‑2 induction and nanoparticle uptake in RAW 264.7 cells, and manipulated adsorption with fucoidan and Pluronic F127. Albumin dominated the protein corona on SWCNTs, and its presence or removal (via fucoidan or Pluronic F127) altered Cox‑2 induction, nanoparticle uptake, and anti‑inflammatory responses, while silica particles exhibited a distinct protein profile and Pluronic F127 pre‑coating reduced serum protein adsorption and toxicity, underscoring the pivotal role of adsorbed proteins in modulating nanomaterial uptake and toxicity.

Abstract

The possible combination of specific physicochemical properties operating at unique sites of action within cells and tissues has led to considerable uncertainty surrounding nanomaterial toxic potential. We have investigated the importance of proteins adsorbed onto the surface of two distinct classes of nanomaterials (single-walled carbon nanotubes [SWCNTs]; 10-nm amorphous silica) in guiding nanomaterial uptake or toxicity in the RAW 264.7 macrophage–like model. Albumin was identified as the major fetal bovine or human serum/plasma protein adsorbed onto SWCNTs, while a distinct protein adsorption profile was observed when plasma from the Nagase analbuminemic rat was used. Damaged or structurally altered albumin is rapidly cleared from systemic circulation by scavenger receptors. We observed that SWCNTs inhibited the induction of cyclooxygenase-2 (Cox-2) by lipopolysaccharide (LPS; 1 ng/ml, 6 h) and this anti-inflammatory response was inhibited by fucoidan (scavenger receptor antagonist). Fucoidan also reduced the uptake of fluorescent SWCNTs (Alexa647). Precoating SWCNTs with a nonionic surfactant (Pluronic F127) inhibited albumin adsorption and anti-inflammatory properties. Albumin-coated SWCNTs reduced LPS-mediated Cox-2 induction under serum-free conditions. SWCNTs did not reduce binding of LPSAlexa488 to RAW 264.7 cells. The profile of proteins adsorbed onto amorphous silica particles (50–1000 nm) was qualitatively different, relative to SWCNTs, and precoating amorphous silica with Pluronic F127 dramatically reduced the adsorption of serum proteins and toxicity. Collectively, these observations suggest an important role for adsorbed proteins in modulating the uptake and toxicity of SWCNTs and nano-sized amorphous silica.