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Small, Volume18, Issue29 July 21, 2022 2202146 | https://doi.org/10.1002/smll.202202146 Fructose-Derived Levan Nanoparticles Protect Against Osteoarthritis by Directly Blocking CD44 Activation

Chanmi Cho, Jin Sil Lee, Hyeryeon Oh, Li-Jung Kang, Yiseul Hwang, Sunyoung Chae, In-Jeong Lee, Seok Jung Kim, Hyunmin Woo, Seong-il Eyun, Ho Chul Kang, Won Il Choi,* and Siyoung Yang*

C. Cho, L.-J. Kang, Y. Hwang, H. C. Kang, S. Yang
Department of Biomedical Sciences Ajou University Graduate School of Medicine Suwon 16499, Republic of Korea

C. Cho, L.-J. Kang, S. Yang
Department of Pharmacology Ajou University School of Medicine Suwon 16499, Republic of Korea

C. Cho, L.-J. Kang, S. Yang
Degenerative InterDiseases Research Center Ajou University School of Medicine Suwon 16499, Republic of Korea

C. Cho, L.-J. Kang, S. Yang
CIRNO Sungkyunkwan University Suwon 16419, Republic of Korea

J. S. Lee, H. Oh, W. I. Choi
Center for Bio-Healthcare Materials Bio-Convergence Materials R&D Division Korea Institute of Ceramic Engineering and Technology Chungbuk 28160, Republic of Korea

J. S. Lee, H. Oh
School of Materials Science and Engineering Gwangju Institute of Science and Technology 123 Cheomdan-gwagiro, Buk-gu, Gwangju 61005, Republic of Korea

Y. Hwang, H. C. Kang
Department of Physiology Ajou University School of Medicine Suwon 16499, Republic of Korea

S. Chae
Institute of Medical Science Ajou University School of Medicine Suwon 16499, Republic of Korea

I.-J. Lee
Three-Dimensional Immune System Imaging Core Facility Ajou University Suwon 16499, Republic of Korea

S. J. Kim
Department of Orthopaedic Surgery College of Medicine The Catholic University of Korea Seoul 06591, Republic of Korea

H. Woo, S.-i. Eyun
Department of Life Science Chung-Ang University Seoul 06974, Republic of Korea

C.C. and J.S.L. contributed equally to this work.

*Corresponding author.

Abstract

Although the development of several inflammatory diseases can be initiated in response to CD44 receptor signaling dysregulation, anti-CD44 antibody therapy has been discontinued in clinical trials owing to its severe adverse effects. Moreover, biocompatible materials that block CD44 are unknown. Here, self-assembled levan nanoparticles (LevNPs) through simple nanoprecipitation without chemical conjugation of biocompatible levan are developed. LevNPs are prepared through a simple nanoprecipitation without chemical conjugation; this results in particles with a consistently dispersed hydrodynamic diameter of approximately 230 nm. The physicochemical properties of LevNP are well-maintained even after long-term storage in a physiological buffer, suggesting that LevNPs are stable and useful for various biomedical applications. A protein array and an in silico LevNP-CD44 interaction assay reveal that LevNPs specifically bind to CD44. Importantly, CD44 is highly expressed in the cartilage of patients with osteoarthritis (OA). LevNPs showed no cytotoxicity and reduced catabolic factor expression in an OA mimic in vitro. Furthermore, intra-articular injection of LevNPs exhibited long-term retention ability in the knee joint and protection against posttraumatic OA cartilage destruction in mice with medial meniscus destabilization–induced OA. These results show that LevNPs are biocompatible and exhibit potential as a nanotherapeutic for protecting against OA pathogenesis by directly blocking CD44.

논문정보

형식Research article
게재일2022년 07월 (BRIC 등록일 2022-09-05)
연구진국내 연구진
분야 의약학 > 면역의학

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