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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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Wang, Miaoyi, Gustafsson, Ove J. R., Siddiqui, Ghizal, Javed, Ibrahim, Kelly, Hannah G., Blin, Thomas, Yin, Hong, Kent, Stephen J., Creek, Darren J., Kempe, Kristian, Ke, Pu Chun and Davis, Thomas P. (2018) Human plasma proteome association and cytotoxicity of nano-graphene oxide grafted with stealth polyethylene glycol and poly(2-ethyl-2-oxazoline). Nanoscale, 10 (23). pp. 10863-10875. doi:10.1039/C8NR00835C

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Official URL: http://dx.doi.org/10.1039/C8NR00835C

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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.

Item Type: Journal Article
Subjects: Q Science > QD Chemistry
T Technology > TP Chemical technology
Divisions: Faculty of Science > Chemistry
Library of Congress Subject Headings (LCSH): Polyethylene glycol, Nanomedicine, Nanobiotechnology
Journal or Publication Title: Nanoscale
Publisher: Royal Society of Chemistry
ISSN: 2040-3364
Official Date: 21 June 2018
Dates:
DateEvent
21 June 2018Published
10 April 2018Available
7 April 2018Accepted
Volume: 10
Number: 23
Page Range: pp. 10863-10875
DOI: 10.1039/C8NR00835C
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
CE140100036Australian Research Councilhttp://dx.doi.org/10.13039/501100000923
Australian Laureate FellowshipAustralian Research Councilhttp://dx.doi.org/10.13039/501100000923
APP1109945National Health and Medical Research Council [NHMRC]http://dx.doi.org/10.13039/501100000925
APP1109945Australian Research Councilhttp://dx.doi.org/10.13039/501100000923

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