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Albumin mediated reactive oxygen species scavenging and targeted delivery of methotrexate for rheumatoid arthritis therapy

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Abstract

Rheumatoid arthritis (RA) is a common chronic systemic autoimmune disease. Although there are a variety of treatments for RA, the substantial clinical therapies are still limited to disease-modifying anti-rheumatic drugs (DMARD), which would induce obvious side-effect in patients after long-term administration. Herein, an uncomplicated drug-induced self-assembly strategy was proposed to fabricate enzyme-loaded albumin nanomedicine. The hydrophobic drug methotrexate (MTX) could induce self-assembly of superoxide dismutase (SOD) and human serum albumin (HSA) to form HSA-SOD-MTX nanoparticle. After intravenous injection, dual-modal imaging including fluorescence imaging or single-photon emission computed tomography (SPECT)/CT imaging exhibits high accumulation of cyanine 5.5 (Cy5.5) or 125I labeled HSA-SOD-MTX nanoparticles in the joints of collagen-induced arthritis (CIA) mice. Importantly, using the synergy therapy of SOD enzyme to scavenge the reactive oxygen species (ROS) and MTX to suppress inflammation, HSA-SOD-MTX nanoparticles exhibit excellent therapeutic efficiency of RA in CIA mice compared with the other groups. Micro-CT and clinical arthritis score of RA mice further demonstrate that RA symptoms of mice treated with HSA-SOD-MTX nanoparticles is significantly relived, which was further demonstrated by the histological analysis and the inflammatory factors measurement. The synergy therapy of inflammation by MTX and SOD enzyme based on HSA-SOD-MTX nanoparticles show excellent therapeutic effects of RA without inducing obvious side effects. Therefore, our strategy may further promote the highly efficient therapy of RA using SOD enzyme to scavenge the ROS and decreasing the side-effect of MTX, which may provide the reference for clinical RA treatment.

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Acknowledgements

This work was partially supported by National Natural Science Foundation of China (Nos. 31822022, U1932208, 31900986, and 81871789), the Natural Science Foundation of Jiangsu Province (Nos. BK20180094 and BK20180052), and a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

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Author notes

  1. Jing Zhong and Qin Zhang contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection & School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu higher Education Institutions, Soochow University, Suzhou, 215123, China

    Jing Zhong, Zheng Zhang, Kexin Shi, Yuanchen Sun, Teng Liu & Kai Yang

  2. Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, 215006, China

    Qin Zhang & Jun Lin

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  1. Jing Zhong
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Correspondence to Jun Lin or Kai Yang.

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Albumin mediated reactive oxygen species scavenging and targeted delivery of methotrexate for rheumatoid arthritis therapy

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Zhong, J., Zhang, Q., Zhang, Z. et al. Albumin mediated reactive oxygen species scavenging and targeted delivery of methotrexate for rheumatoid arthritis therapy. Nano Res. 15, 153–161 (2022). https://doi.org/10.1007/s12274-021-3449-1

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  • DOI: https://doi.org/10.1007/s12274-021-3449-1

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