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Synergistic Oxygen Generation and Reactive Oxygen Species Scavenging by Manganese Ferrite/Ceria Co-decorated Nanoparticles for Rheumatoid Arthritis Treatment

Cited 22 time in Web of Science Cited 23 time in Scopus
Authors
Kim, Jonghoon; Kim, Han Young; Song, Seuk Young; Go, Seok-hyeong; Sohn, Hee Su; Baik, Seungmin; Soh, Min; Kim, Kang; Kim, Dokyoon; Kim, Hyo-Cheol; Lee, Nohyun; Kim, Byung-Soo; Hyeon, Taeghwan
Issue Date
2019-03
Citation
ACS Nano, Vol.13 No.3, pp.3206-3217
Keywords
manganese ferrite nanoparticlesoxygen generationmacrophage polarizationrheumatoid arthritisnanomedicine
Abstract
Poor O-2 supply to the infiltrated immune cells in the joint synovium of rheumatoid arthritis (RA) up-regulates hypoxia-inducible factor (HIF-1 alpha) expression and induces reactive oxygen species (ROS) generation, both of which exacerbate synovial inflammation. Synovial inflammation in RA can be resolved by eliminating pro-inflammatory M1 macrophages and inducing anti-inflammatory M2 macrophages. Because hypoxia and ROS in the RA synovium play a crucial role in the induction of Ml macrophages and reduction of M2 macrophages, herein, we develop manganese ferrite and ceria nanoparticle-anchored mesoporous silica nanoparticles (MFC-MSNs) that can synergistically scavenge ROS and produce O-2 for reducing M1 macrophage levels and inducing M2 macrophages for RA treatment. MFC-MSNs exhibit a synergistic effect on O-2 generation and ROS scavenging that is attributed to the complementary reaction of ceria nanoparticles (NPs) that can scavenge intermediate hydroxyl radicals generated by manganese ferrite NPs in the process of O-2 generation during the Fenton reaction, leading to the efficient polarization of M1 to M2 macrophages both in vitro and in vivo. Intra-articular administration of MFC-MSNs to rat RA models alleviated hypoxia, inflammation, and pathological features in the joint. Furthermore, MSNs were used as a drug-delivery vehicle, releasing the anti-rheumatic drug methotrexate in a sustained manner to augment the therapeutic effect of MFC-MSNs. This study highlights the therapeutic potential of MFC-MSNs that simultaneously generate O-2 and scavenge ROS, subsequently driving inflammatory macrophages to the anti-inflammatory subtype for RA treatment.
ISSN
1936-0851
URI
http://hdl.handle.net/10371/165767
DOI
https://doi.org/10.1021/acsnano.8b08785
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College of Engineering/Engineering Practice School (공과대학/대학원)Dept. of Chemical and Biological Engineering (화학생물공학부)Journal Papers (저널논문_화학생물공학부)
College of Engineering/Engineering Practice School (공과대학/대학원)Dept. of Chemical and Biological Engineering (화학생물공학부)Chemical Convergence for Energy and Environment (에너지환경 화학융합기술전공)Journal Papers (저널논문_에너지환경 화학융합기술전공)
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