A Dual‐Responsive Fe₃O₄@ZIF‐8 Nanoplatform Combining Magnetic Targeting and pH Sensitivity for Low Back Pain Therapy

Low back pain (LBP) resulting from sciatic nerve compression presents major challenges in pain management, as traditional therapies provide only short-term relief and pose risks of systemic toxicity. In this study, an innovative Fe₃O₄@ZIF-8-RVC (FZR) dual-responsive nanoplatform is introduced that integrates magnetic targeting with pH-sensitive, sustained drug release to overcome these limitations. The FZR nanoplatform encapsulates ropivacaine (RVC) within the ZIF-8-coated Fe₃O₄ core, enabling precise and prolonged analgesia at the injury site through magnetic guidance and acid-triggered release. In vitro and in vivo assessments indicate that FZR achieves high drug loading, sustained release in acidic environments, and excellent biocompatibility, significantly extending analgesic effects in chronic nerve injury models while minimizing systemic exposure. Behavioral tests and molecular analyses in LBP rat models confirm that FZR effectively suppresses pain-related neuronal activity and central sensitization markers. This dual-responsive nanoplatform FZR offers a safe, long-lasting, and targeted therapeutic approach, holding strong potential for advancing pain relief in LBP and related neuropathic pain conditions.