Variations in biocorona formation related to defects in the structure of single walled carbon nanotubes and the hyperlipidemic disease state

Achyut J Raghavendra,Sherleen Fu,Ramakrishna Podila,Jonathan H Shannahan,Jared M Brown,Kristofer Fritz

doi:10.1038/s41598-017-08896-w

Abstract

Ball-milling utilizes mechanical stress to modify properties of carbon nanotubes (CNTs) including size, capping, and functionalization. Ball-milling, however, may introduce structural defects resulting in altered CNT-biomolecule interactions. Nanomaterial-biomolecule interactions result in the formation of the biocorona (BC), which alters nanomaterial properties, function, and biological responses. The formation of the BC is governed by the nanomaterial physicochemical properties and the physiological environment. Underlying disease states such as cardiovascular disease can alter the biological milieu possibly leading to unique BC identities. In this ex vivo study, we evaluated variations in the formation of the BC on single-walled CNTs (SWCNTs) due to physicochemical alterations in structure resulting from ball-milling and variations in the environment due to the high-cholesterol disease state. Increased ball-milling time of SWCNTs resulted in enhanced structural defects. Following incubation in normal mouse serum, label-free quantitative proteomics identified differences in the biomolecular content of the BC due to the ball-milling process. Further, incubation in cholesterol-rich mouse serum resulted in the formation of unique BCs compared to SWCNTs incubated in normal serum. Our study demonstrates that the BC is modified due to physicochemical modifications such as defects induced by ball-milling and physiological disease conditions, which may result in variable biological responses.

Highlights

Single walled carbon nanotubes (SWCNTs) are one-dimensional structures with unique optical and electronic properties relevant for many biomedical applications[1,2,3]
It has been previously shown that intensive ball milling for ~50 h completely disrupts single-walled CNTs (SWCNTs) tubular structure leading to multi-layered polyaromatic carbon materials[28]
A strong PL emission was observed for all SWCNTs ~1560 nm when excited at 1064 nm. This observation suggests that the one-dimensional tubular structure of SWCNTs, necessary for the presence of van Hove singularities (vHS), was retained in all the ball milled samples

Summary

Introduction

Single walled carbon nanotubes (SWCNTs) are one-dimensional structures with unique optical and electronic properties relevant for many biomedical applications[1,2,3]. The addition of the BC alters the surface and properties of the SWCNTs but may modify their cellular interactions similar to what has been shown with other nanoparticles[13,14,15,16,17] This means that the BC can interfere with the intended biological applications of SWCNTs (viz., imaging or drug delivery) by altering their biodistribution, clearance, and/or toxicity. This unique BC on Fe3O4 NPs that formed in high cholesterol serum exacerbated the inflammatory response of endothelial cells following exposure, when compared to Fe3O4 NPs with a normal serum BC26 This finding demonstrates that disease-induced alterations in the physiological environment can impact NP biological response by altering the BC. Thereby, based on these observations, it is imperative to evaluate differences in the BC that forms under these increasingly prominent disease states for a comprehensive assessment of nanotoxicity

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Results

Conclusion