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      Cloaking nanoparticles with protein corona shield for targeted drug delivery

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          Abstract

          Targeted drug delivery using nanoparticles can minimize the side effects of conventional pharmaceutical agents and enhance their efficacy. However, translating nanoparticle-based agents into clinical applications still remains a challenge due to the difficulty in regulating interactions on the interfaces between nanoparticles and biological systems. Here, we present a targeting strategy for nanoparticles incorporated with a supramolecularly pre-coated recombinant fusion protein in which HER2-binding affibody combines with glutathione- S-transferase. Once thermodynamically stabilized in preferred orientations on the nanoparticles, the adsorbed fusion proteins as a corona minimize interactions with serum proteins to prevent the clearance of nanoparticles by macrophages, while ensuring systematic targeting functions in vitro and in vivo. This study provides insight into the use of the supramolecularly built protein corona shield as a targeting agent through regulating the interfaces between nanoparticles and biological systems.

          Abstract

          The efficacy of nanoparticles can be significantly inhibited by serum proteins binding to them. Here, the author developed a supramolecularly constructed protein corona on nanoparticles, which minimises interactions with serum proteins to prevent the clearance of these particles by macrophages.

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          Most cited references32

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          Analysis of nanoparticle delivery to tumours

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            Understanding and controlling the interaction of nanomaterials with proteins in a physiological environment.

            Nanomaterials hold promise as multifunctional diagnostic and therapeutic agents. However, the effective application of nanomaterials is hampered by limited understanding and control over their interactions with complex biological systems. When a nanomaterial enters a physiological environment, it rapidly adsorbs proteins forming what is known as the protein 'corona'. The protein corona alters the size and interfacial composition of a nanomaterial, giving it a biological identity that is distinct from its synthetic identity. The biological identity determines the physiological response including signalling, kinetics, transport, accumulation, and toxicity. The structure and composition of the protein corona depends on the synthetic identity of the nanomaterial (size, shape, and composition), the nature of the physiological environment (blood, interstitial fluid, cell cytoplasm, etc.), and the duration of exposure. In this critical review, we discuss the formation of the protein corona, its structure and composition, and its influence on the physiological response. We also present an 'adsorbome' of 125 plasma proteins that are known to associate with nanomaterials. We further describe how the protein corona is related to the synthetic identity of a nanomaterial, and highlight efforts to control protein-nanomaterial interactions. We conclude by discussing gaps in the understanding of protein-nanomaterial interactions along with strategies to fill them (167 references).
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              Protein adsorption is required for stealth effect of poly(ethylene glycol)- and poly(phosphoester)-coated nanocarriers

              The current gold standard to reduce non-specific cellular uptake of drug delivery vehicles is by covalent attachment of poly(ethylene glycol) (PEG). It is thought that PEG can reduce protein adsorption and thereby confer a stealth effect. Here, we show that polystyrene nanocarriers that have been modified with PEG or poly(ethyl ethylene phosphate) (PEEP) and exposed to plasma proteins exhibit a low cellular uptake, whereas those not exposed to plasma proteins show high non-specific uptake. Mass spectrometric analysis revealed that exposed nanocarriers formed a protein corona that contains an abundance of clusterin proteins (also known as apolipoprotein J). When the polymer-modified nanocarriers were incubated with clusterin, non-specific cellular uptake could be reduced. Our results show that in addition to reducing protein adsorption, PEG, and now PEEPs, can affect the composition of the protein corona that forms around nanocarriers, and the presence of distinct proteins is necessary to prevent non-specific cellular uptake.
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                Author and article information

                Contributors
                chaekyu@unist.ac.kr
                sabsab7@unist.ac.kr
                jhryu@unist.ac.kr
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                31 October 2018
                31 October 2018
                2018
                : 9
                : 4548
                Affiliations
                [1 ]ISNI 0000 0004 0381 814X, GRID grid.42687.3f, Department of Chemistry, , Ulsan National Institute of Science and Technology (UNIST), ; Ulsan, 44919 Republic of Korea
                [2 ]ISNI 0000 0004 0381 814X, GRID grid.42687.3f, Department of Biological Sciences, , Ulsan National Institute of Science and Technology (UNIST), ; Ulsan, 44919 Republic of Korea
                [3 ]ISNI 0000 0004 0381 814X, GRID grid.42687.3f, Department of Energy Engineering, School of Energy and Chemical Engineering, , Ulsan National Institute of Science and Technology (UNIST), ; Ulsan, 44919 Republic of Korea
                [4 ]ISNI 0000 0004 0381 814X, GRID grid.42687.3f, In Vivo Research Center, UNIST, Central Research Facilities, , Ulsan National Institute of Science and Technology (UNIST), ; Ulsan, 44919 Republic of Korea
                Author information
                http://orcid.org/0000-0002-0332-1534
                http://orcid.org/0000-0002-3269-6095
                http://orcid.org/0000-0003-0252-0985
                Article
                6979
                10.1038/s41467-018-06979-4
                6208370
                30382085
                88101734-be45-4fd6-8150-6e3d906926ff
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 14 May 2018
                : 3 October 2018
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100003725, National Research Foundation of Korea (NRF);
                Award ID: 2015H1D3A1061983
                Award ID: 2018R1A6A1A03025810
                Award ID: 2016R1A5A1009405
                Award ID: 2017R1A2B4003617
                Award Recipient :
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