Effective Treatment of Knee Osteoarthritis Using a Nano‐Enabled Drug Acupuncture Technology in Mice

Abstract A nano‐enabled drug delivery acupuncture technology ( nd ‐Acu) is developed that is based on traditional acupuncture needles where the stainless‐steel surface is designed to deliver various payload molecules. To create the nd ‐Acu platform, an electrochemistry procedure is used to attach methyl salicylate‐modified cyclodextrin in which the sugar rings allow the encapsulation of structurally defined single or multiple payload molecules via an inclusion complexation process. Drug loading and release profile are first studied using fluorescent dyes abiotically and at intact animal level. nd ‐Acu allows more efficient dye loading and time‐dependent release compared to pristine needles without cyclodextrin modification. Subsequently, a proof‐of‐principle efficacy study is conducted using the platform to load a local anesthetic, lidocaine, for the treatment of knee osteoarthritis (KOA) in mice. It is demonstrated that lidocaine‐laden nd ‐Acu can effectively alleviate pain, reduce inflammation, and slow down KOA development biochemically and histologically. Hypothesis‐driven and proteomic approaches are utilized to investigate the working mechanisms of lidocaine nd ‐Acu, indicating that the therapeutic outcome is attributed to the in vivo modulation of the HMGB1/TLR4 signaling pathway. The study also obtained preliminary evidence suggesting the involvement of mitochondria as well as small GTPase such as cdc42 during the treatment by lidocaine nd ‐Acu.