Penghao Ji, Chengjie Li, Yang Tang, Jiachang Hong, Wei Liu, Dongliang Huo, Shixiong Kang, Rongmin Dun, Fei Zhu, Liying Wang, Shutong Liu, Qihui Wu, Peng Wu, Minfeng Huo, Jianlin Shi
Inflammatory arthritis is a chronic immune disorder characterized by synovial inflammation, pain, and progressive joint destruction, yet most current therapies focus on the regulation of a single pathological process or symptom. In the present work, we report the establishment of self-assembled strontium-caffeic acid nanoparticles (CA-Sr NPs) through metal-polyphenol coordination, which function as an integrated neuro-immune-bone modulator for inflammatory arthritis therapy. By coupling redox catalysis with TRPV1-associated Ca2+ antagonism and Sr2+-enabled osteoregulation, CA-Sr NPs exhibit combined effects of sustained reactive oxygen species scavenging and enhanced regulation of the Ca2+-permeable TRPV1 channel on macrophages and dorsal root ganglion (DRG) neurons, thus repolarizing macrophages from M1 to M2 phenotype and suppressing the pathological Ca2+ influx and neuronal hyperexcitability, respectively. Meanwhile, CA-Sr NPs promote osteoblast activity while inhibiting osteoclast differentiation. In the Complete Freund's Adjuvant-induced murine arthritis model, CA-Sr NPs markedly alleviated multiple inflammatory arthritis symptoms, including joint swelling, pain, and bone erosion. Collectively, this study highlights highly promising therapeutic potentials of CA-Sr NPs for inflammatory arthritis management and broadens the scope of metal-phenolic nanocatalysts toward treating neuro-immune-bone disorders.