한빛사논문
Chanmi Cho a,1, Hyeryeon Oh b,c,1, Jin Sil Lee b,c, Li-Jung Kang d,e,f, Eun-Jeong Oh d,f, Yiseul Hwang d,g, Seok Jung Kim h, Yong-Soo Bae a, Eun-Jeong Kim i,****, Ho Chul Kang d,g,***, Won Il Choi b,**, Siyoung Yang a,*
a Department of Biological Sciences, Sungkyunkwan University, Suwon, 16419, Republic of Korea
b Center for Bio-Healthcare Materials, Bio-Convergence Materials R&D Division, Korea Institute of Ceramic Engineering and Technology, 202, Osongsaengmyeong 1-ro,
Osong-eup, Heungdeok-gu, Cheongju, Chungbuk, 28160, Republic of Korea
c School of Materials Science and Engineering, Gwangju Institute of Science and Technology, 123 Cheomdan-gwagiro, Buk-gu, Gwangju, 61005, Republic of Korea
d Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, 16499, Republic of Korea
e AI-Superconvergence KIURI Translational Research Center, Ajou University School of Medicine, Suwon, 16499, Republic of Korea
f Department of Pharmacology, Ajou University School of Medicine, Suwon, 16499, Republic of Korea
g Department of Physiology, Ajou University School of Medicine, Suwon, Gyeonggi, 16499, Republic of Korea
h Department of Orthopedic Surgery, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea
i Department of Life Science, Chung-Ang University, Seoul, 06974, Republic of Korea
1 These authors contributed equally to this paper as co-first authors.
Corresponding authors.: Eun-Jeong Kim, Ho Chul Kang, Won Il Choi, Siyoung Yang
Abstract
Osteoarthritis (OA) is a degenerative joint disorder associated with inflammation, functional disability, and high socioeconomic costs. The development of effective therapies against inflammatory OA has been limited owing to its complex and multifactorial nature. The efficacy of Prussian blue nanozymes coated with Pluronic (PPBzymes), US Food and Drug Administration-approved components, and their mechanisms of action have been described in this study, and PPBzymes have been characterized as a new OA therapeutic. Spherical PPBzymes were developed via nucleation and stabilization of Prussian blue inside Pluronic micelles. A uniformly distributed diameter of approximately 204 nm was obtained, which was maintained after storage in an aqueous solution and biological buffer. This indicates that PPBzymes are stable and could have biomedical applications. In vitro data revealed that PPBzymes promote cartilage generation and reduce cartilage degradation. Moreover, intra-articular injections with PPBzymes into mouse joints revealed their long-term stability and effective uptake into the cartilage matrix. Furthermore, intra-articular PPBzymes injections attenuated cartilage degradation without exhibiting cytotoxicity toward the synovial membrane, lungs, and liver. Notably, based on proteome microarray data, PPBzymes specifically block the JNK phosphorylation, which modulates inflammatory OA pathogenesis. These findings indicate that PPBzymes might represent a biocompatible and effective nanotherapeutic for obstructing JNK phosphorylation.
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