Ultrasound/Acidity‐Triggered and Nanoparticle‐Enabled Analgesia

Abstract Local anesthetics have been extensively employed to treat postoperative pain, but they generally suffer from short acting duration and potential neurotoxicity under high local concentrations, which require the controlled and sustained releasing patterns of treatment drugs. In this work, it is reported, for the first time, the construction of hollow mesoporous organosilica nanoparticles (HMONs)‐based nanoplatforms for localized delivery and controlled/sustained release of loaded ropivacaine for local anesthetics, which can be repeatedly triggered by either external ultrasound irradiation or acidity triggering to release the payload, causing on‐demand and long‐lasting analgesia. Based on the in vivo mouse model of incision pain, the controlled and sustained release of ropivacaine achieves more than six hours of continuous analgesia, which is almost three times longer as compared to single free ropivacaine injection. The low neurotoxicity and high biocompatibility of HMONs for nanoparticle‐enabled analgesia are also demonstrated both in vitro and in vivo. This designed/constructed HMONs‐based nanoplatform provides a potential methodology for clinical pain management via on‐demand and long‐lasting pain relief.