A synergistic nanozyme platform breaking the neuroinflammatory-oxidative stress cycle for extended pain relief

Chronic inflammatory pain represents a major public health burden driven by a vicious, self-perpetuating cycle of neuroinflammation and oxidative stress within the central nervous system. Effective clinical management critically requires targeted therapeutics with long-lasting efficacy. Herein, we report a novel liposome-based co-delivery system (SeCQDs@Liposome-RA, SLR) encapsulating a selenium-doped carbon quantum dot (SeCQD) nanozyme and the potent anti-inflammatory agent raddeanin A (RA). This platform was rationally engineered for synergistic antioxidant and anti-inflammatory actions. In vitro, SLR nanoparticles efficiently neutralized free radicals and significantly reduced pro-inflammatory cytokines in activated microglia. Crucially, leveraging the liposome's sustained-release capabilities, a single dose of SLR provided profound and durable analgesia in a Complete Freund's Adjuvant-induced inflammatory pain mouse model, lasting up to 72 hours. Mechanistically, this extended effect is achieved by SLR's dual inhibition of the mitogen-activated protein kinase and nuclear factor kappa B signaling pathways, thereby reversing microglial activation. This strategy not only significantly extends the duration of pain relief but also presents a robust, rationally designed co-delivery platform for efficient management of chronic inflammatory diseases.