Sulfoxide-Containing Polymer-Coated Nanoparticles Demonstrate Minimal Protein Fouling and Improved Blood Circulation
Sulfoxide-Containing Polymer-Coated Nanoparticles Demonstrate Minimal Protein Fouling and Improved Blood Circulation
Minimizing the interaction of nanomedicines with the mononuclear phagocytic system (MPS) is a critical challenge for their clinical translation. Conjugating polyethylene glycol (PEG) to nanomedicines is regarded as an effective approach to reducing the sequestration of nanomedicines by the MPS. However, recent concerns about the immunogenicity of PEG highlight the demand of alternative low-fouling polymers as innovative coating materials for nanoparticles. Herein, a highly hydrophilic sulfoxide-containing polymer—poly(2-(methylsulfinyl)ethyl acrylate) (PMSEA)—is used for the surface coating of iron oxide nanoparticles (IONPs). It is found that the PMSEA polymer coated IONPs have a more hydrophilic surface than their PEGylated counterparts, and demonstrate remarkably reduced macrophage cellular uptake and much less association with human plasma proteins. In vivo study of biodistribution and pharmacokinetics further reveals a much-extended blood circulation (≈2.5 times longer in terms of elimination half-life t1/2) and reduced accumulation (approximately two times less) in the organs such as the liver and spleen for IONPs coated by PMSEA than those by PEG. It is envisaged that the highly hydrophilic sulfoxide-containing polymers have huge potential to be employed as an advantageous alternative to PEG for the surface functionalization of a variety of nanoparticles for long circulation and improved delivery.
long circulation, low-fouling, nanoparticles, sulfoxide-containing polymers
Qiao, Ruirui
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Fu, Changkui
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Li, Yuhuan
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Qi, Xiaole
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Ni, Dalong
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Nandakumar, Aparna
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Siddiqui, Ghizal
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Wang, Haiyan
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Zhang, Zheng
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Wu, Tingting
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Zhong, Jian
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Tang, Shi Yang
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Pan, Shuaijun
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Zhang, Cheng
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Whittaker, Michael R.
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Engle, Jonathan W.
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Creek, Darren J.
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Caruso, Frank
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Ke, Pu Chun
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Cai, Weibo
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Whittaker, Andrew K.
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Davis, Thomas P.
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1 July 2020
Qiao, Ruirui
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Fu, Changkui
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Li, Yuhuan
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Qi, Xiaole
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Ni, Dalong
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Nandakumar, Aparna
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Siddiqui, Ghizal
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Wang, Haiyan
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Zhang, Zheng
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Wu, Tingting
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Zhong, Jian
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Tang, Shi Yang
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Pan, Shuaijun
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Zhang, Cheng
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Whittaker, Michael R.
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Engle, Jonathan W.
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Creek, Darren J.
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Caruso, Frank
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Ke, Pu Chun
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Cai, Weibo
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Whittaker, Andrew K.
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Davis, Thomas P.
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Qiao, Ruirui, Fu, Changkui, Li, Yuhuan, Qi, Xiaole, Ni, Dalong, Nandakumar, Aparna, Siddiqui, Ghizal, Wang, Haiyan, Zhang, Zheng, Wu, Tingting, Zhong, Jian, Tang, Shi Yang, Pan, Shuaijun, Zhang, Cheng, Whittaker, Michael R., Engle, Jonathan W., Creek, Darren J., Caruso, Frank, Ke, Pu Chun, Cai, Weibo, Whittaker, Andrew K. and Davis, Thomas P.
(2020)
Sulfoxide-Containing Polymer-Coated Nanoparticles Demonstrate Minimal Protein Fouling and Improved Blood Circulation.
Advanced Science, 7 (13), [2000406].
(doi:10.1002/advs.202000406).
Abstract
Minimizing the interaction of nanomedicines with the mononuclear phagocytic system (MPS) is a critical challenge for their clinical translation. Conjugating polyethylene glycol (PEG) to nanomedicines is regarded as an effective approach to reducing the sequestration of nanomedicines by the MPS. However, recent concerns about the immunogenicity of PEG highlight the demand of alternative low-fouling polymers as innovative coating materials for nanoparticles. Herein, a highly hydrophilic sulfoxide-containing polymer—poly(2-(methylsulfinyl)ethyl acrylate) (PMSEA)—is used for the surface coating of iron oxide nanoparticles (IONPs). It is found that the PMSEA polymer coated IONPs have a more hydrophilic surface than their PEGylated counterparts, and demonstrate remarkably reduced macrophage cellular uptake and much less association with human plasma proteins. In vivo study of biodistribution and pharmacokinetics further reveals a much-extended blood circulation (≈2.5 times longer in terms of elimination half-life t1/2) and reduced accumulation (approximately two times less) in the organs such as the liver and spleen for IONPs coated by PMSEA than those by PEG. It is envisaged that the highly hydrophilic sulfoxide-containing polymers have huge potential to be employed as an advantageous alternative to PEG for the surface functionalization of a variety of nanoparticles for long circulation and improved delivery.
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Published date: 1 July 2020
Additional Information:
Funding Information:
R.Q., C.F., and Y.L. contributed equally to this work. This work was supported by the Australian Research Council Centre of Excellence in Convergent Bio‐Nano Science and Technology (project number CE140100036). R.Q. acknowledges the financial support from National Health and Medical Research Council (APP1158755) and National Natural Science Foundation of China (81571746). A.W. acknowledges the financial support from Australian Research Council (CE140100036, DP0987407, DP110104299, DP180101221, LE0775684, LE0668517, and LE0882357) and the National Health and Medical Research Council (APP1021759). C.F. acknowledges the University of Queensland for a UQ Development Fellowship (UQFEL1831361). C.Z. acknowledges the National Health and Medical Research Council for his Early Career Fellowship (APP1157440). W.C. acknowledges the financial support from the National Institutes of Health (P30CA014520). The Australian National Fabrication Facility, Queensland Node, is also acknowledged for access to some items of equipment. The authors acknowledge the Monash Biomedical Proteomics and Metabolomics Facility, Monash University, for the provision of instrumentation, training, and technical support.
Funding Information:
R.Q., C.F., and Y.L. contributed equally to this work. This work was supported by the Australian Research Council Centre of Excellence in Convergent Bio-Nano Science and Technology (project number CE140100036). R.Q. acknowledges the financial support from National Health and Medical Research Council (APP1158755) and National Natural Science Foundation of China (81571746). A.W. acknowledges the financial support from Australian Research Council (CE140100036, DP0987407, DP110104299, DP180101221, LE0775684, LE0668517, and LE0882357) and the National Health and Medical Research Council (APP1021759). C.F. acknowledges the University of Queensland for a UQ Development Fellowship (UQFEL1831361). C.Z. acknowledges the National Health and Medical Research Council for his Early Career Fellowship (APP1157440). W.C. acknowledges the financial support from the National Institutes of Health (P30CA014520). The Australian National Fabrication Facility, Queensland Node, is also acknowledged for access to some items of equipment. The authors acknowledge the Monash Biomedical Proteomics and Metabolomics Facility, Monash University, for the provision of instrumentation, training, and technical support.
Publisher Copyright:
© 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Keywords:
long circulation, low-fouling, nanoparticles, sulfoxide-containing polymers
Identifiers
Local EPrints ID: 481727
URI: http://eprints.soton.ac.uk/id/eprint/481727
ISSN: 2198-3844
PURE UUID: 11aede2e-d523-47ef-a3ab-8be123003027
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Date deposited: 06 Sep 2023 16:53
Last modified: 18 Mar 2024 04:13
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Contributors
Author:
Ruirui Qiao
Author:
Changkui Fu
Author:
Yuhuan Li
Author:
Xiaole Qi
Author:
Dalong Ni
Author:
Aparna Nandakumar
Author:
Ghizal Siddiqui
Author:
Haiyan Wang
Author:
Zheng Zhang
Author:
Tingting Wu
Author:
Jian Zhong
Author:
Shi Yang Tang
Author:
Shuaijun Pan
Author:
Cheng Zhang
Author:
Michael R. Whittaker
Author:
Jonathan W. Engle
Author:
Darren J. Creek
Author:
Frank Caruso
Author:
Pu Chun Ke
Author:
Weibo Cai
Author:
Andrew K. Whittaker
Author:
Thomas P. Davis
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