Audrey Paoletti, Bineta Ly, Catherine Cailleau, Fan Gao, Marie Péan de Ponfilly-Sotier, Juliette Pascaud, Elodie Rivière, Luxin Yang, Lilian Nwosu, Aziza Elmesmari, Franceline Reynaud, Magali Hita, David Paterson, Julien Reboud, Francois Fay, Gaetane Nocturne, Nicolas Tsapis, Iain B. McInnes, Mariola Kurowska-Stolarska, Elias Fattal, Xavier Mariette
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In this study, we employed two preclinical models of RA, collagen-induced arthritis and K/BxN serum transfer arthritis, to examine the therapeutic potential of antagomiR-155-5p entrapped within PEGylated (polyethylene glycol [PEG]) liposomes in resolution of arthritis and repolarization of monocytes towards the anti-inflammatory M2 phenotype.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>AntagomiR-155-5p or antagomiR-control were encapsulated in PEG liposomes of 100 nm in size and −10 mV in zeta potential with high antagomiR loading efficiency (above 80%). Mice were injected intravenously with 1.5 nmol/100 μL PEG liposomes containing antagomiR-155-5p or control after the induction of arthritis.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>We demonstrated the biodistribution of fluorescently tagged PEG liposomes to inflamed joints one hour after the injection of fluorescently tagged PEG liposomes, as well as the liver's subsequent accumulation after 48 hours, indicative of hepatic clearance, in mice with arthritis. The injection of PEG liposomes containing antagomiR-155-5p decreased arthritis score and paw swelling compared with PEG liposomes containing antagomiR-control or the systemic delivery of free antagomiR-155-5p. Moreover, treatment with PEG liposomes containing antagomiR-155-5p led to the restoration of bone marrow monocyte defects in anti-inflammatory macrophage differentiation without any significant functional change in other immune cells, including splenic B and T cells.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>The injection of antagomiR-155-5p encapsulated in PEG liposomes allows the delivery of small RNA to monocytes and macrophages and reduces joint inflammation in murine models of RA, providing a promising strategy in human disease.</p>\n \n <div>\n <figure>\n <div><picture>\n <source></source></picture><p></p>\n </div>\n </figure>\n </div>\n </section>\n </div>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"76 1","pages":"18-31"},"PeriodicalIF":11.4000,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/art.42665","citationCount":"1","resultStr":"{\"title\":\"Liposomal AntagomiR-155-5p Restores Anti-Inflammatory Macrophages and Improves Arthritis in Preclinical Models of Rheumatoid Arthritis\",\"authors\":\"Audrey Paoletti, Bineta Ly, Catherine Cailleau, Fan Gao, Marie Péan de Ponfilly-Sotier, Juliette Pascaud, Elodie Rivière, Luxin Yang, Lilian Nwosu, Aziza Elmesmari, Franceline Reynaud, Magali Hita, David Paterson, Julien Reboud, Francois Fay, Gaetane Nocturne, Nicolas Tsapis, Iain B. 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Liposomal AntagomiR-155-5p Restores Anti-Inflammatory Macrophages and Improves Arthritis in Preclinical Models of Rheumatoid Arthritis
Objective
We previously reported an increased expression of microRNA-155 (miR-155) in the blood monocytes of patients with rheumatoid arthritis (RA) that could be responsible for impaired monocyte polarization to anti-inflammatory M2-like macrophages. In this study, we employed two preclinical models of RA, collagen-induced arthritis and K/BxN serum transfer arthritis, to examine the therapeutic potential of antagomiR-155-5p entrapped within PEGylated (polyethylene glycol [PEG]) liposomes in resolution of arthritis and repolarization of monocytes towards the anti-inflammatory M2 phenotype.
Methods
AntagomiR-155-5p or antagomiR-control were encapsulated in PEG liposomes of 100 nm in size and −10 mV in zeta potential with high antagomiR loading efficiency (above 80%). Mice were injected intravenously with 1.5 nmol/100 μL PEG liposomes containing antagomiR-155-5p or control after the induction of arthritis.
Results
We demonstrated the biodistribution of fluorescently tagged PEG liposomes to inflamed joints one hour after the injection of fluorescently tagged PEG liposomes, as well as the liver's subsequent accumulation after 48 hours, indicative of hepatic clearance, in mice with arthritis. The injection of PEG liposomes containing antagomiR-155-5p decreased arthritis score and paw swelling compared with PEG liposomes containing antagomiR-control or the systemic delivery of free antagomiR-155-5p. Moreover, treatment with PEG liposomes containing antagomiR-155-5p led to the restoration of bone marrow monocyte defects in anti-inflammatory macrophage differentiation without any significant functional change in other immune cells, including splenic B and T cells.
Conclusion
The injection of antagomiR-155-5p encapsulated in PEG liposomes allows the delivery of small RNA to monocytes and macrophages and reduces joint inflammation in murine models of RA, providing a promising strategy in human disease.
期刊介绍：
Arthritis & Rheumatology is the official journal of the American College of Rheumatology and focuses on the natural history, pathophysiology, treatment, and outcome of rheumatic diseases. It is a peer-reviewed publication that aims to provide the highest quality basic and clinical research in this field. The journal covers a wide range of investigative areas and also includes review articles, editorials, and educational material for researchers and clinicians. Being recognized as a leading research journal in rheumatology, Arthritis & Rheumatology serves the global community of rheumatology investigators and clinicians.
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