Designing a theranostic probe for noninvasive bone imaging and bone disease therapy is both challenging and desirable.Herein,an ultrasmall Au nanocluster(NC,<2 nm)-based theranostic probe is developed to achieve hi...Designing a theranostic probe for noninvasive bone imaging and bone disease therapy is both challenging and desirable.Herein,an ultrasmall Au nanocluster(NC,<2 nm)-based theranostic probe is developed to achieve highly temporospatial in vivo bone-targeted photoluminescence(PL)imaging in the second near-infrared window(NIR-Ⅱ)and enhanced rheumatoid arthritis(RA)therapy.The key design of the probe involves the surface phosphorylation of atomically precise NIR-Ⅱemitting Au_(44)NCs.This phosphorylation enhances the bone-targeting ability of the probe due to the highly concentrated phosphate groups,allowing the probe to realize in vivo bone-targeted NIR-ⅡPL imaging.Moreover,benefiting from the enhanced bone-targeting ability,ultrasmall hydrodynamic diameter,and excellent anti-inflammation and immunomodulatory effects,the probe not only demonstrates superior therapeutic efficacy for RA rats,effectively restoring the destructed cartilage to nearly normal but also exhibits good renal clearance and benign biocompatibility.These favorable attributes cannot be achieved by commercial methotrexate used for RA treatment.This study presents a new design paradigm for metal NC-based theranostic probes,offering the potential for high-resolution bone-targeted PL imaging and improved RA therapy.展开更多
基金National Natural Science Foundation of China,Grant/Award Number:22071127Taishan Scholar Foundation of Shandong Province,Grant/Award Number:tsqn201812074Natural Science Foundation of Shandong Province,Grant/Award Number:ZR2019YQ07。
文摘Designing a theranostic probe for noninvasive bone imaging and bone disease therapy is both challenging and desirable.Herein,an ultrasmall Au nanocluster(NC,<2 nm)-based theranostic probe is developed to achieve highly temporospatial in vivo bone-targeted photoluminescence(PL)imaging in the second near-infrared window(NIR-Ⅱ)and enhanced rheumatoid arthritis(RA)therapy.The key design of the probe involves the surface phosphorylation of atomically precise NIR-Ⅱemitting Au_(44)NCs.This phosphorylation enhances the bone-targeting ability of the probe due to the highly concentrated phosphate groups,allowing the probe to realize in vivo bone-targeted NIR-ⅡPL imaging.Moreover,benefiting from the enhanced bone-targeting ability,ultrasmall hydrodynamic diameter,and excellent anti-inflammation and immunomodulatory effects,the probe not only demonstrates superior therapeutic efficacy for RA rats,effectively restoring the destructed cartilage to nearly normal but also exhibits good renal clearance and benign biocompatibility.These favorable attributes cannot be achieved by commercial methotrexate used for RA treatment.This study presents a new design paradigm for metal NC-based theranostic probes,offering the potential for high-resolution bone-targeted PL imaging and improved RA therapy.