Fluorine-modified polymers reduce the adsorption of immune-reactive proteins to PEGylated gold nanoparticles.

Content Provider	Europe PMC
Author	Forgham, Helen Zhu, Jiayuan Zhang, Taoran Huang, Xumin Li, Xiangke Shen, Ao Biggs, Heather Talbo, Gert Xu, Chun Davis, Thomas P Qiao, Ruirui
Copyright Year	2024
Description	Aim: To investigate the influence of fluorine in reducing the adsorption of immune-reactive proteins onto PEGylated gold nanoparticles. Methods: Reversible addition fragmentation chain transfer polymerization, the Turkevich method and ligand exchange were used to prepare polymer-coated gold nanoparticles. Subsequent in vitro physicochemical and biological characterizations and proteomic analysis were performed. Results: Fluorine-modified polymers reduced the adsorption of complement and other immune-reactive proteins while potentially improving circulatory times and modulating liver toxicity by reducing apolipoprotein E adsorption. Fluorine actively discouraged phagocytosis while encouraging the adsorption of therapeutic targets, CD209 and signaling molecule calreticulin. Conclusion: This study suggests that the addition of fluorine in the surface coating of nanoparticles could lead to improved performance in nanomedicine designed for the intravenous delivery of cargos. Summary pointsThe aim of this study was to investigate the influence of fluorine in reducing the adsorption of complement and other immune-reactive proteins onto PEGylated gold nanoparticles (AuNPs).Reversible addition fragmentation chain transfer polymerization, the Turkevich method and ligand exchange were used to prepare AuNPs capped with polymers containing 0, 3, 6, 15 and 30% fluorine.In vitro physicochemical and biological validations were performed to determine the necessary physiological parameters for each of the AuNPs.Proteomics was performed to characterize the protein corona fingerprint for each of the five AuNPs.The adsorption of complement proteins was significantly decreased at 3% fluorine relative to 0% fluorine. The greatest reduction in adsorption was observed at 30% fluorine.Important immune-reactive proteins (immunoglobulins and platelet basic protein) are also less adsorbed in the presence of fluorine.Fluorine significantly reduced phagocytosis by macrophages.CD209 preferentially adsorbs to fluorine-capped AuNPs, suggesting potential future applications for fluorinated polymers as a microbicide or providing a targeted approach for NP delivery of gene therapies aimed at colon cancer.Calreticulin preferentially adsorbs to fluorine-capped AuNPs, opening up opportunities for NP-led attempts to improve local antitumor immunity.Collectively, this work successfully illustrates the rationale for more widespread investigation of fluorine during the development of polymer-coated NPs designed for the intravenous delivery of nanomedicines. Plain language summaryNanomedicines are based around the delivery of therapies by tiny, nanosized delivery vehicles. This method offers a much better way of specifically targeting life-threatening diseases. For fast delivery, nanomedicines can be injected into the blood (intravenously); however, this often leads to an unwanted and exaggerated immune response. The immune system is activated by proteins in the blood that attach themselves to nanoparticles through various chemical interactions (the protein corona effect). Fluorine is a chemical routinely used in surfactants such as firefighting foam and more recently in molecular imaging and nanoparticles designed for the delivery of therapies aimed at cancer. While fluorine has great potential to improve the cellular uptake of therapies, little is known about whether it can also help camouflage the nanoparticles against the immune system responses. Here, using fluorinated polymer-coated gold nanoparticles, the authors demonstrate that fluorine reduces uptake by immune cells and is highly effective at reducing the binding of immune system-initiating proteins. This work successfully illustrates the rationale for more widespread investigation of fluorine during the development of polymer-coated nanoparticles designed for the intravenous delivery of nanomedicines. Tweetable abstractFluorine-modified polymer coatings on gold nanoparticles exhibit greater antifouling effects against complement and other immunogenic proteins found in the blood.
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Page Count	18
ISSN	17435889
Volume Number	19
DOI	10.2217/nnm-2023-0357
PubMed Central reference number	PMC11221377
Issue Number	11
PubMed reference number	38593053
Journal	Nanomedicine [Nanomedicine (Lond)]
e-ISSN	17486963
Language	English
Publisher	Taylor & Francis
Publisher Date	2024-04-09
Access Restriction	Open
Rights License	This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent. © 2024 The Authors
Subject Keyword	fluorination gold immune evasion nanoparticles polymers protein corona
Content Type	Text
Resource Type	Article
Subject	Nanoscience and Nanotechnology Medicine Development Bioengineering Materials Science Biomedical Engineering