Ultrasound‐Propelled Antioxidant Nanobowls for the Treatment of Osteoarthritis

Abstract Osteoarthritis is a major global health concern, characterized by progressive degradation of articular cartilage and excessive accumulation of reactive oxygen species (ROS). Although intra‐articular drug delivery is a commonly employed therapeutic approach, its effectiveness is often hindered by the dense and avascular structure of the cartilage matrix. To overcome this limitation, ultrasound‐propelled MnO ₂ ‐decorated nanobowls (Mn‐nanobowls) are developed, capable of directional movement within joint tissues. These nanobowls are synthesized via self‐assembly of P(AzoAA ₂₄ ‐ stat ‐MAA ₁₀ ), facilitated by π – π interactions and hydrogen bonding, followed by in situ deposition of MnO ₂ nanoparticles onto their surface. The MnO ₂ decoration endows nanobowls with ROS‐scavenging properties and simultaneous oxygen generation. Furthermore, the Mn‐nanobowls exhibit strong catalase‐like enzymatic activity, achieving ≈25% hydrogen peroxide decomposition at a MnO ₂ concentration of 5 µg mL ⁻¹ , comparable to that of free MnO ₂ particles. Under ultrasound irradiation, the Mn‐nanobowls demonstrate directional propulsion at a speed of 40.35 µm s ⁻¹ in vitro. In vivo studies indicate that ultrasound‐propelled Mn‐nanobowls can penetrate deeply into the dense cartilage matrix, up to 307 µm, substantially improving therapeutic delivery compared to passive diffusion. Overall, this study introduces a promising and innovative strategy for osteoarthritis treatment through ultrasound‐propelled nanocarriers with enhanced tissue penetration and multifunctional ROS‐scavenging capabilities.