2. Academic Validation
  3. A ROS-responsive microsphere capsule encapsulated with NADPH oxidase 4 inhibitor ameliorates macrophage inflammation and ferroptosis

A ROS-responsive microsphere capsule encapsulated with NADPH oxidase 4 inhibitor ameliorates macrophage inflammation and ferroptosis

  • Heliyon. 2023 Dec 12;10(1):e23589. doi: 10.1016/j.heliyon.2023.e23589.
Jinze Zhen 1,  Tianhao Wan 1,  Guangxin Sun 2,  Xinwei Chen 1,  Shanyong Zhang 1
Affiliations

Affiliations

  • 1 Department of Oral Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology, Shanghai, 200011, China.
  • 2 Department of Oral and Maxillofacial Surgery, School of Stomatology, China Medical University, Oral Diseases Laboratory of Liaoning, Shenyang, 110000, China.
PMID: 38187270 DOI: 10.1016/j.heliyon.2023.e23589
Abstract

Inflammatory macrophages within the synovium play a pivotal role in the progression of arthritis inflammation. Effective drug therapy targeting inflammatory macrophages has long been a goal for clinicians and researchers. The standard approach for treating osteoarthritis (OA) involves systemic treatment and local injection. However, the high incidence of side effects associated with long-term drug administration increases the risk of complications in patients. Additionally, the rapid clearance of the joint cavity poses a biological barrier to the therapeutic effect. NADPH Oxidase 4 (NOX4) is an enzyme protein regulating the cellular redox state by generating Reactive Oxygen Species (ROS) within the cell. In this study, we designed and fabricated a hydrogel microsphere consisting of methyl methacrylate (MMA) and polyvinyl acetate (PVA) as the outer layer structure. We then loaded GLX351322 (GLX), a novel selective NOX4 Inhibitor, into hydrogel microspheres through self-assembly with the compound polyethylene glycol ketone mercaptan (mPEG-TK) containing a disulfide bond, forming nanoparticles (mPEG-TK-GLX), thus creating a two-layer drug-loaded microspheres capsule with ROS-responsive and slow-releasing capabilities. Our results demonstrate that mPEG-TK-GLX@PVA-MMA effectively suppressed TBHP-induced inflammation, ROS production, and Ferroptosis, indicating a promising curative strategy for OA and Other inflammatory diseases in the future.

Keywords

Biomaterials; Ferroptosis; Macrophage inflammation; NOX4; Nanoparticles.

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