Liposomal antagomiR-155-5p restores anti-inflammatory macrophages and improves arthritis in preclinical models of rheumatoid arthritis

Paoletti, A. et al. (2024) Liposomal antagomiR-155-5p restores anti-inflammatory macrophages and improves arthritis in preclinical models of rheumatoid arthritis. Arthritis and Rheumatology, 76(1), pp. 18-31. (doi: 10.1002/art.42665) (PMID:37527031)

Abstract

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.image

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McInnes, Professor Iain and Yang, Miss Luxin and Kurowska-Stolarska, Professor Mariola and Gao, Fan and Elmesmari, Dr Aziza and Paoletti, Dr Audrey and Reboud, Professor Julien and Paterson, Mr David
• Authors: Paoletti, A., Ly, B., Cailleau, C., Gao, F., de Ponfilly‐Sotier, M. P., Pascaud, J., Rivière, E., Yang, L., Nwosu, L., Elmesmari, A., Reynaud, F., Hita, M., Paterson, D., Reboud, J., Fay, F., Nocturne, G., Tsapis, N., McInnes, I. B., Kurowska-Stolarska, M., Fattal, E., and Mariette, X.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Science and Engineering > School of Engineering > Biomedical Engineering
• Journal Name: Arthritis and Rheumatology
• Publisher: Wiley
• ISSN: 2326-5191
• ISSN (Online): 2326-5205
• Published Online: 01 July 2023
• Copyright Holders: Copyright © 2023 The Authors
• First Published: First published in Arthritis and Rheumatology 76(1):18-31
• Publisher Policy: Reproduced under a Creative Commons licence