Magnesium hexacyanoferrate nanocatalysts alleviates fibromyalgia syndrome by reversing cellular ferroptosis

Fibromyalgia (FM), the most common causes of chronic musculoskeletal pain, is a complex syndrome with an indefinite etiology. Ferroptosis is a new type of cell death characterized by iron-dependent lipid peroxidation, affecting many chronic pain diseases. Here, we confirmed the role of ferroptosis in FM using a mouse model of reserpine induction. Then, we developed polyvinylpyrrolidone-assembled magnesium hexacyanoferrate nanocatalysts (MgHCF NCs) as a new type of ferroptosis inhibitor, for its efficacy in ferrous ions capture and antioxidation. Excellent in vivo FM-alleviation effect from MgHCF NCs was demonstrated. The FM-protective and antiferroptotic efficacy of MgHCF NCs at the transcriptional level were explored by whole-transcriptome analysis. Meanwhile, the remarkable antiferroptotic effect of MgHCF NCs was further validated in vitro ferroptosis-inducer experiments, which was firmly associated with the efficacy of MgHCF NCs on reducing oxidative stress, mitochondrial protection and correcting disordered polyunsaturated fatty acids (PUFAs) metabolism. The excellent antiferroptotic effect and biocompatibility render MgHCF NCs to be highly promising and clinically transformable agents for FM treatment