Marcela Frota Cavalcante, Márcia Duarte Adorne, Walter Miguel Turato, Marina Kemmerer, Mayara Klimuk Uchiyama, Ana Carolina Cavazzin Asbahr, Aline de Cristo Soares Alves, Sandra Helena Poliselli Farsky, Carine Drewes, Marina Cecília Spatti, Soraya Megumi Kazuma, Marcel Boß, Silvia Stanisçuaski Guterres, Koiti Araki, Bernhard Brüne, Dmitry Namgaladze, Adriana Raffin Pohlmann, Dulcineia Saes Parra Abdalla
- Atherosclerosis can be originated from the accumulation of modified cholesterol-rich lipoproteins in the arterial wall. The electronegative LDL, LDL(-), plays an important role in the pathogenesis of atherosclerosis once this cholesterol-rich lipoprotein can be internalized by macrophages, contributing to the formation of foam cells, and provoking an immune-inflammatory response. Herein, we engineered a nanoformulation containing highly pure surface-functionalized nanocapsules using a single-chain fragment variable (scFv) reactive to LDL(-) as a ligand and assessed whether it can affect the LDL(-) uptake by primary macrophages and the progression of atherosclerotic lesions in Ldlr−/− mice. The engineered and optimized scFv-anti-LDL(-)-MCMN-Zn nanoformulation is internalized by human and murine macrophages in vitro by different endocytosis mechanisms. Moreover, macrophages exhibited lower LDL(-) uptake and reduced mRNA and protein levels of IL1B and MCP1 induced by LDL(-) when treated with this new nanoformulation. In a mouse model of atherosclerosis employing Ldlr−/− mice, intravenous administration of scFv-anti-LDL(-)-MCMN-Zn nanoformulation inhibited atherosclerosis progression without affecting vascular permeability or inducing leukocytes-endothelium interactions. Together, these findings suggest that a scFv-anti-LDL(-)-MCMN-Zn nanoformulation holds promise to be used in future preventive and therapeutic strategies for atherosclerosis.
MetadatenAuthor: | Marcela Frota Cavalcante, Márcia Duarte Adorne, Walter Miguel Turato, Marina KemmererGND, Mayara Klimuk UchiyamaORCiD, Ana Carolina Cavazzin Asbahr, Aline de Cristo Soares Alves, Sandra Helena Poliselli FarskyORCiD, Carine DrewesORCiD, Marina Cecília Spatti, Soraya Megumi KazumaORCiD, Marcel BoßGND, Silvia Stanisçuaski Guterres, Koiti Araki, Bernhard BrüneORCiD, Dmitry NamgaladzeORCiD, Adriana Raffin PohlmannORCiD, Dulcineia Saes Parra AbdallaORCiD |
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URN: | urn:nbn:de:hebis:30:3-620387 |
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DOI: | https://doi.org/10.3389/fmed.2021.652137 |
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ISSN: | 2296-858X |
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Parent Title (English): | Frontiers in medicine |
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Publisher: | Frontiers Media |
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Place of publication: | Lausanne |
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Document Type: | Article |
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Language: | English |
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Date of Publication (online): | 2021/04/20 |
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Date of first Publication: | 2021/04/20 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2023/01/09 |
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Tag: | atherosclerosis; electronegative LDL; macrophage; nanocapsules; nanoformulation; single chain fragment variable |
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Volume: | 8 |
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Issue: | art. 652137 |
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Article Number: | 652137 |
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Page Number: | 14 |
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First Page: | 1 |
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Last Page: | 14 |
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Note: | This research was supported by FAPESP (São Paulo Research Foundation, grant 2012/51316-5 to DA and scholarships to MC and SK) and CNPq (National Council for Scientific and Technological Development: grant to the National Institute of Science and Technology for Pharmaceutical Innovation, INCT_if, and Universal Project to AP and SG), Brazil. |
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Institutes: | Biochemie, Chemie und Pharmazie / Biochemie und Chemie |
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Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Licence (German): | Creative Commons - CC BY - Namensnennung 4.0 International |
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