Dual-switched carbon monoxide nano gas tank for auto-diagnosis and precision therapy of osteoarthritis

Carbon monoxide (CO) has great potential in the therapy of osteoarthritis (OA), but its controllable delivery in vivo is still an intractable problem. To optimize CO gas therapy for OA, a stable CO release platform with multi-stimulus responsiveness must be designed. Herein, we describe a local delivery system (Fe3(CO)12 @Croc-PEG5K) for near-infrared fluorescence (NIRF) imaging-guided photothermal treatment and CO gas synergistic therapy. As a nano gas tank, Fe3(CO)12 @Croc-PEG5K releases CO on-demand under near infrared (NIR) laser irradiation, scavenges free radicals and regulates the pH in the OA microenvironment, and relieves the in-flammatory response of macrophages to maintain the vitality of chondrocytes. Furthermore, the pH-dependent NIRF imaging properties of Fe3(CO)12 @Croc-PEG5K can be exploited to determine the administration interval and auto-monitor the curative effects during the therapeutic process. Owing to these merits, the photothermal and CO gas synergistic therapy mediated by Fe3(CO)12 @Croc-PEG5K can be optimized to deliver outstanding therapeutic performance in vivo, as demonstrated by the OA rat model. Our study is the first to validate the therapeutic effect of CO against OA in vivo, reveals a promising strategy for precision medicine pertaining to the treatment of OA and broadens the scope of CO gas therapy.