Mimicking Antioxidases And Hyaluronan Synthase: A Novel Zwitterionic Nanozyme for Photothermal Therapy of Osteoarthritis.

Restoring joint homeostasis is crucial for relieving osteoarthritis (OA). Current strategies are limited to unilateral efforts in joint lubrication, inhibition of inflammation, free radicals scavenging, and cartilage regeneration. Herein, by modifying molybdenum disulfide (MoS 2 ) with Mg 2+ -doped polydopamine and coating with polysulfobetaines, we constructed a dual-bionic photothermal nanozyme (MPMP) to mimic antioxidases/hyaluronan synthase for OA therapy. Photothermally enhanced lubrication lowered the coefficient of friction (0.028) in the early stage of OA treatment. The antioxidases-mimicking properties of MPMP nanozyme contributed to eliminating ROS/RNS (over 90% of scavenging ratio for H 2 O 2 /·OH/O·-2/DPPH/ABTS + ) and supplying O 2 . With NIR irradiation, MPMP nanozyme triggered thermogenesis (upregulating HSP70 expression) and Mg 2+ release, which promoted the chondrogenesis in inflammatory conditions by deactivating of NF-κB/IL-17 signaling pathways and enhancing MAPK signaling pathway. Benefiting from HSP70 and Mg 2+ , MPMP-NIR showed HAS-mimicking activity to increase the intracellular (2.00-fold) and extracellular (3.12-fold) HA production. Therefore, MPMP-NIR demonstrated superior spatiotemporally therapeutic effect on OA in mice model, in terms of osteophytes (83.41% reduction), OARSI scores (88.57% reduction) and ACAN expression (2.70-fold increment). Hence, insights into dual-bionic nanozymes can be a promising strategy for OA therapy or other inflammation-related diseases. This article is protected by copyright. All rights reserved.