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Issue 23, 2018
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Human plasma proteome association and cytotoxicity of nano-graphene oxide grafted with stealth polyethylene glycol and poly(2-ethyl-2-oxazoline)

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Abstract

Polyethylene glycol (PEG) is a gold standard against protein fouling. However, recent studies have revealed surprising adverse effects of PEG, namely its immunogenicity and shortened bio-circulation upon repeated dosing. This highlights a crucial need to further examine ‘stealth’ polymers for controlling the protein ‘corona’, a new challenge in nanomedicine and bionanotechnology. Poly(2-ethyl-2-oxazoline) (PEtOx) is another primary form of stealth polymer that, despite its excellent hydrophilicity and biocompatibility, has found considerably less applications compared with PEG. Herein, we performed label-free proteomics to compare the associations of linear PEG- and PEtOx-grafted nano-graphene oxide (nGO) sheets with human plasma proteins, complemented by cytotoxicity and haemolysis assays to compare the cellular interactions of these polymers. Our data revealed that nGO-PEG enriched apolipoproteins, while nGO-PEtOx displayed a preferred binding with pro-angiogenic and structural proteins, despite high similarities in their respective top-10 enriched proteins. In addition, nGO-PEG and nGO-PEtOx exhibited similar levels of enrichment of complement proteins. Both PEG and PEtOx markedly reduced nGO toxicity to HEK 293 cells while mitigating nGO haemolysis. This study provides the first detailed profile of the human plasma protein corona associated with PEtOx-grafted nanomaterials and, in light of the distinctions of PEtOx in chemical adaptability, in vivo clearance and immunogenicity, validates the use of PEtOx as a viable stealth alternative to PEG for nanomedicines and bionanotechnologies.

Graphical abstract: Human plasma proteome association and cytotoxicity of nano-graphene oxide grafted with stealth polyethylene glycol and poly(2-ethyl-2-oxazoline)

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Publication details

The article was received on 30 Jan 2018, accepted on 07 Apr 2018 and first published on 10 Apr 2018


Article type: Paper
DOI: 10.1039/C8NR00835C
Citation: Nanoscale, 2018,10, 10863-10875
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    Human plasma proteome association and cytotoxicity of nano-graphene oxide grafted with stealth polyethylene glycol and poly(2-ethyl-2-oxazoline)

    M. Wang, O. J. R. Gustafsson, G. Siddiqui, I. Javed, H. G. Kelly, T. Blin, H. Yin, S. J. Kent, D. J. Creek, K. Kempe, P. C. Ke and T. P. Davis, Nanoscale, 2018, 10, 10863
    DOI: 10.1039/C8NR00835C

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