程亮教授及其合作者在natl. sci. rev.上发表论文-尊龙凯时

作者：

shunyi lu^1,2#, yuqi yang^2#, zhuorun song^1,2#, jie cao², zhihui han², linfu chen², yunfei he³, jiayi wang⁴, yun teng¹, zengli zhang⁵, jun zou¹*, jun ge^1,2*, huilin yang¹* and liang cheng²*

单位：

¹department of orthopedic surgery, the first affiliated hospital of soochow university, suzhou 215123, china.

²institute of functional nano & soft materials (funsom), jiangsu key laboratory for carbon-based functional materials and devices, soochow university, suzhou 215123, china.

³soochow university institues for translational medicine, the first affiliated hospital of soochow university, suzhou 215123, china.

⁴department of orthopedic surgery, shanghai jiao tong university affiliated sixth people's hospital, shanghai 200233, china.

⁵department of environmental health school of public health, soochow university, suzhou 215123, china.

摘要：

osteosarcoma (os), a highly aggressive bone tumor, presents significant challenges in terms of effective treatment. we identified that cellular autophagy was impaired within os by comparing clinical os samples through bioinformatic analyses and further validated the inhibition of mitochondrial autophagy in os at the transcriptomic level. based on this finding, we investigated the therapeutic potential of a dual functional metal nanoplatform (mns_x) to facilitate a transition from the protective effect of low-level autophagy in os to the killing effect of high-level autophagy in os. mns_x facilitated intracellular h₂s generation via endocytosis, leading to the s-sulfhydration of ubiquitin-specific peptidase 8 (usp8) and subsequent promotion of mitochondrial autophagy in vitro. additionally, mns_x activated the cyclic guanosine monophosphate–adenosine monophosphate synthase (cgas)–stimulator of interferon genes (sting) pathway, further enhancing the cellular autophagic response and accelerating tumor cell death. moreover, it was demonstrated in vivo that mns_x, on the one hand, mediated the activation of tumor autophagy by usp8 via intracellular h₂s, while mn² promoted the maturation of dendritic cells, activated cytotoxic t lymphocytes and contributed to tumor eradication. such tumor killing could be suppressed by the autophagy inhibitor chloroquine. importantly, synergistic combination therapy with immune checkpoint inhibitors showed promise for achieving complete remission of os. this study highlights the potential of mns_x as a dual-functional therapeutic platform for os treatment and offers novel directions for future research in this field.

影响因子：

16.3

分区情况：

一区

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