| 论文简介 |
Methicillin-resistant Staphylococcus aureus (MRSA) is threating human health due to its resistance to multiple antibiotics. Excessive Cu ions target the lipoylated proteins of tricarboxylic acid cycle of cancer cells, inducing proteotoxic stress and their cuproptosis death. Whether cuproptosis plays a part in killing MRSA by low-dose supplement of Cu ions remains to be explored. Herein, Cu doped hydroxyapatite nanorods (PC) are prepared on polyetheretherketone (PEEK) to resist infection and improve PEEK performance in tissue integration with the assistance of near infrared (NIR) irradiation, and the mechanism against MRSA is elucidated. Mild photothermal stimulation increases bacterial membrane permeability, accelerating Cu ions’ intake and consequently inducing cuproptosis-like death of MRSA. It is confirmed by aggregation of dihydrolipoamide S-acetyltrans-ferase (DLAT), deactivation of glutathione peroxides 4 (GPX4) and destabilization of Fe-S cluster proteins ferredoxin (FDX1) and lipoyl synthase (LIAS). Fortunately, fibroblast behaviors are upregulated on NIR irradiated PC. In vivo, PC with NIR irradiation exhibits outstanding MRSA elimination, reduced inflammation response and improved biointegration. Overall, it is demonstrated that bacterial cuproptosis-like death can be induced by Cu ions at a non-cytotoxic dose when cooperated with mild thermal stimulus, and this photothermal strategy of PC has greatly promising application in improving performance of PEEK in clinic. |
(创新港)
