Authors
Wanying Zhai, Xinyang Mao, Aixian Tian, Jing Jia, Zukang Miao, Aidong Liu, Ning Zhao, Zheng Wang, Xiujie Zhao, Xin Li, Xinlong Ma, Yanjun Zhao
Published in
Biomaterials. Volume 338. Issue Pt A. Pages 124606. Sep 01, 2026. Epub Sep 01, 2026.
Abstract
The involvement of oxidative stress, inflammation, and energy metabolism disorders in osteoarthritis (OA) makes it challenging to handle these problems using a single therapeutic agent concurrently. Here, we report a tailored bioactive conjugate consisting of a hydrophobic radical-trapping antioxidant (vitamin E, VE), a hydrophilic nicotinamide adenine dinucleotide (NAD+), and a reactive oxygen species (ROS)-responsive phenylboronic acid linker. The conjugate self-assembly produced VE-NAD+ nanoparticles with high drug loading (>90%), a small hydrodynamic size (ca. 60 nm), and good kinetic stability. The nanoparticles significantly increased intracellular NAD+ levels, inhibited lipid peroxidation and oxidative stress, and suppressed pro-inflammatory cytokine release in macrophages (RAW 264.7) and rat chondrocytes in vitro. The multifunctional nanoparticles also down-regulated the key matrix metalloproteinases. Upon intra-articular delivery, the VE-NAD+ nanoparticles potently mitigated synovial inflammation and alleviated cartilage damage in a spontaneous OA mouse model, as evidenced by magnetic resonance imaging, histological staining, critical biomarker quantification, and OA grading assessment. This work provides an innovative disease-modifying approach to OA management, which may have applications in other aging-related disorders.
PMID:
42700728
Bibliographic data and abstract were imported from PubMed on 06 Sep 2026.
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