Treatment of Rheumatoid Arthritis Based on the Inherent Bioactivity of Black Phosphorus Nanosheets.

Rheumatoid arthritis (RA) is an autoimmune disease that affects the living quality of patients, especially the elderly population. RA-related morbidity and mortality increase significantly with age, while current clinical drugs for RA are far from satisfactory and may have serious side effects. Therefore, the development of new drugs with higher biosafety and efficacy is demanding. Black phosphorus nanosheets (BPNSs) have been widely studied because of their excellent biocompatibility. Here, we focus on the inherent bioactivity of BPNSs, report the potential of BPNSs as a therapeutic drug for RA and elucidate the underlying therapeutic mechanism. We find that BPNSs inhibit autophagy at an early stage via the AMPK-mTOR pathway, switch the energy metabolic pathway to oxidative phosphorylation, increase intracellular ATP levels, suppress apoptosis, reduce inflammation and oxidative stress, and down-regulate senescence-associated secretory phenotype (SASP)-related genes in rheumatoid arthritis synovial fibroblasts (RA-SFs). Further, BPNSs induce the apoptosis of macrophages and promote their transition from the M1 to the M2 phenotype by regulating related cytokines. Significantly, the administration of BPNSs can alleviate key pathological features of RA in mice, revealing great therapeutic potential. This study provides a novel option for treating RA, with BPNSs emerging as a promising therapeutic candidate.