Development of nanoparticles incorporated with quercetin and ACE2-membrane as a novel therapy for COVID-19
Jia-You Fang, Kuo-Yen Huang, Tong-Hong Wang, Zih-Chan Lin, Chin-Chuan Chen, Sui-Yuan Chang, En-Li Chen, Tai-Ling Chao, Shuenn-Chen Yang, Pan-Chyr Yang, Chi-Yuan Chen
Journal of Nanobiotechnology, doi:10.1186/s12951-024-02435-2
Introduction Angiotensin-converting enzyme 2 (ACE2) and AXL tyrosine kinase receptor are known to be involved in the SARS-CoV-2 entry of the host cell. Therefore, targeting ACE2 and AXL should be an effective strategy to inhibit virus entry into cells. However, developing agents that can simultaneously target ACE2 and AXL remains a formidable task. The natural compound quercetin has been shown to inhibit AXL expression.
Materials and methods In this study, we employed PLGA nanoparticles to prepare nanoparticles encapsulated with quercetin, coated with ACE2-containing cell membranes, or encapsulated with quercetin and then coated with ACE-2-containing cell membranes. These nanoparticles were tested for their abilities to neutralize or inhibit viral infection.
Results Our data showed that nanoparticles encapsulated with quercetin and then coated with ACE2-containing cell membrane inhibited the expression of AXL without causing cytotoxic activity. Nanoparticles incorporated with both quercetin and ACE2-containing cell membrane were found to be able to neutralize pseudo virus infection and were more effective than free quercetin and nanoparticles encapsulated with quercetin at inhibition of pseudo virus and SARS-CoV-2 infection.
Conclusions We have shown that the biomimetic nanoparticles incorporated with both ACE-2 membrane and quercetin showed the most antiviral activity and may be further explored for clinical application.
Data availability All data generated for this study are included in the article.
Declarations Ethics approval and consent to participate The study involving SARS-CoV-2 was approved by the National Taiwan University Hospital Research Ethics Committee (202002002RIND). All of the mouse experiments were approved by the Institutional Animal Care and Use Committee (IACUC) of Chang Gung University (IACUC approval no.: CGU110-015) and Chang Gung Memorial Hospital (IACUC approval no.: 2020121704).
Consent for publication Not applicable.
Competing interests The authors declare no competing interests.
Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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"abstract": "<jats:title>Abstract</jats:title><jats:sec>\n <jats:title>Introduction</jats:title>\n <jats:p>Angiotensin-converting enzyme 2 (ACE2) and AXL tyrosine kinase receptor are known to be involved in the SARS-CoV-2 entry of the host cell. Therefore, targeting ACE2 and AXL should be an effective strategy to inhibit virus entry into cells. However, developing agents that can simultaneously target ACE2 and AXL remains a formidable task. The natural compound quercetin has been shown to inhibit AXL expression.</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Materials and methods</jats:title>\n <jats:p>In this study, we employed PLGA nanoparticles to prepare nanoparticles encapsulated with quercetin, coated with ACE2-containing cell membranes, or encapsulated with quercetin and then coated with ACE-2-containing cell membranes. These nanoparticles were tested for their abilities to neutralize or inhibit viral infection.</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Results</jats:title>\n <jats:p>Our data showed that nanoparticles encapsulated with quercetin and then coated with ACE2-containing cell membrane inhibited the expression of AXL without causing cytotoxic activity. Nanoparticles incorporated with both quercetin and ACE2-containing cell membrane were found to be able to neutralize pseudo virus infection and were more effective than free quercetin and nanoparticles encapsulated with quercetin at inhibition of pseudo virus and SARS-CoV-2 infection.</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Conclusions</jats:title>\n <jats:p>We have shown that the biomimetic nanoparticles incorporated with both ACE-2 membrane and quercetin showed the most antiviral activity and may be further explored for clinical application.</jats:p>\n </jats:sec>",
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