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

Miaoyi Wang, Ove J.R. Gustafsson, Ghizal Siddiqui, Ibrahim Javed, Hannah G. Kelly, Thomas Blin, Hong Yin, Stephen J. Kent, Darren J. Creek, Kristian Kempe, Pu Chun Ke, Thomas P. Davis

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Pages (from-to)10863-10875
Number of pages13
JournalNanoscale
Volume10
Issue number23
DOIs
Publication statusPublished - 21 Jun 2018

Cite this

@article{c23134cbfd4f4155a7fd5a6dec2b1eb8,
title = "Human plasma proteome association and cytotoxicity of nano-graphene oxide grafted with stealth polyethylene glycol and poly(2-ethyl-2-oxazoline)",
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.",
author = "Miaoyi Wang and Gustafsson, {Ove J.R.} and Ghizal Siddiqui and Ibrahim Javed and Kelly, {Hannah G.} and Thomas Blin and Hong Yin and Kent, {Stephen J.} and Creek, {Darren J.} and Kristian Kempe and Ke, {Pu Chun} and Davis, {Thomas P.}",
year = "2018",
month = "6",
day = "21",
doi = "10.1039/c8nr00835c",
language = "English",
volume = "10",
pages = "10863--10875",
journal = "Nanoscale",
issn = "2040-3364",
publisher = "The Royal Society of Chemistry",
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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). / 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; Davis, Thomas P.

In: Nanoscale, Vol. 10, No. 23, 21.06.2018, p. 10863-10875.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Human plasma proteome association and cytotoxicity of nano-graphene oxide grafted with stealth polyethylene glycol and poly(2-ethyl-2-oxazoline)

AU - Wang, Miaoyi

AU - Gustafsson, Ove J.R.

AU - Siddiqui, Ghizal

AU - Javed, Ibrahim

AU - Kelly, Hannah G.

AU - Blin, Thomas

AU - Yin, Hong

AU - Kent, Stephen J.

AU - Creek, Darren J.

AU - Kempe, Kristian

AU - Ke, Pu Chun

AU - Davis, Thomas P.

PY - 2018/6/21

Y1 - 2018/6/21

N2 - 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.

AB - 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.

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U2 - 10.1039/c8nr00835c

DO - 10.1039/c8nr00835c

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JF - Nanoscale

SN - 2040-3364

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