Authors
Xueying An, Hantao Cai, Wenshu Wu, Minyi Cai, Yu Ben, Tao Shen, Pan Zhang, Jianmei Chen, Zhihong Xu, Qing Jiang
Published in
Bioactive materials. Volume 67. Pages 22-37. Epub Jul 31, 2026.
Abstract
Osteoarthritis (OA) arises from chondrocyte senescence driven by intertwined oxidative stress and abnormal m6A methylation, with few treatments targeting both pathological pathways. Lycopene, an antioxidant, is limited by poor bioavailability, whereas Wilms tumor 1-associating protein (WTAP), a core m6A methyltransferase, has no specific inhibitors. Herein, we fabricated cartilage-targeted HPcLW nanoparticles (∼250 nm) via electrostatic self-assembly of human serum albumin (HSA) and poly-L-lysine (PLL) with collagen II-binding peptide, co-loaded with lycopene and WTAP siRNA. The targeting modification extended joint fluorescence retention to 10 days after intra-articular injection with good serum stability and biosafety. In aged mice and medial meniscus (DMM)-induced OA mouse models, intra-articular HPcLW attenuated cartilage degeneration, restored COL2 expression, and suppressed MMP13 levels. Mechanistically, WTAP siRNA suppressed m6A modification to downregulate PAI-1 expression, while lycopene scavenged ROS and protected siRNA integrity, cooperatively disrupting the WTAP/PAI-1 axis and alleviating mitochondrial dysfunction. By integrating antioxidant and epigenetic strategies, HPcLW counteracts the senescence loop, establishing the WTAP/PAI-1 axis as a therapeutic target and highlighting co-delivery nanomedicine for age-related joint diseases.
PMID:
42571396
Bibliographic data and abstract were imported from PubMed on 09 Aug 2026.
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