A simple endogenous zinc-activated and accumulated nanocluster platform for memory immunotherapy of spinal cord injury

Spinal cord injury (SCI) can cause very serious bodily harm or even paralysis. However, all clinical drugs require long-term use to relieve the disease, causing toxicity and side effects. Zinc tends to activate the self-defense system to repair SCI, but the currently reported zinc supplementation is not efficient to cure SCI due to the poor targeting effects. The zinc delivery system has been employed to improve the targeting efficiency, which also increases the complexity and toxicity of drugs. On the other hand, we envisage that if there is a drug that can accumulate and activate endogenous zinc in the lesions of the spinal cord and stimulate immunotherapy, it can not only reduce long-term drug dependence but also significantly improve the therapeutic effect on SCI. Herein, we found zinc deficiency for SCI mice, but more zinc accumulated in the lesions of the spinal cord after the administration of GSH-AuNCs in SCI mice. Meanwhile, more microglia/macrophages polarize toward M2 from M1 phenotypes after zinc accumulation which enhances immunotherapy effects. Thereafter, the inflammatory response was inhibited, which exerts a neuroprotective effect. As well as this, the current treatment showed memory effects for zinc accumulation even after stopping the drug administration, allowing endogenous zinc to continue its induction of multiple therapeutic effects. Due to the direct and memory curative function, the lesions of SCI mice were well recovered and the motor functions were also significantly improved.