题目： | self-cascaded pyroptosis-sting initiators for catalytic metalloimmunotherapy |
作者： | qiao yu1,3#, shumin sun1#, nailin yang1,2*, zifan pei1, youdong chen1, jihu nie1, huali lei1, li wang1, fei gong1, and liang cheng1,2* |
单位： | 1institute of functional nano & soft materials (funsom), jiangsu key laboratory for carbon-based functional materials and devices, soochow university, suzhou 215123, china. 2macao institute of materials science and engineering, macau university of science and technology, macau sar 999078, china. 3state key laboratory of advanced drug delivery and release systems, zhejiang provincial key laboratory for advanced drug delivery systems, college of pharmaceutical sciences, zhejiang university, hangzhou 310058, china. |
摘要： | gasdermin (gsdm)-mediated pyroptosis involves the induction of mitochondrial damage and the subsequent release of mitochondrial dna (mtdna), which is anticipated to activate the cgas-sting pathway, thereby augmenting the antitumor immune response. however, challenges lie in effectively triggering pyroptosis in cancer cells and subsequently enhancing the cgas-sting activation with specificity. herein, we developed intelligent self-cascaded pyroptosis-sting initiators of cobalt fluoride (cof2) nanocatalysts for catalytic metalloimmunotherapy. cof2 nanocatalysts with a semiconductor structure and enzyme-like activity generated a substantial amount of reactive oxygen species (ros) under stimulation by endogenous h2o2 and exogenous ultrasound. importantly, we discovered that co-based nanomaterials themselves induce pyroptosis in cancer cells. therefore, cof2 nanocatalysts initially acted as pyroptosis inducers, triggering caspase-1/gsdmd-dependent pyroptosis in cancer cells via co2 and ros, leading to mtdna release. subsequently, cof2 nanocatalysts were further utilized as intelligent sting agonists that were specifically capable of detecting mtdna and augmenting the activation of the cgas-sting pathway. these cascade events triggered a robust immune response, effectively modulating the immunosuppressive tumor microenvironment into an immune-supportive state, thereby providing favorable support for antitumor therapy. this innovative strategy not only significantly impeded the growth of the primary tumor but also elicited an immune response to further augment the efficacy of immune checkpoint inhibitors in preventing distant tumor progression. overall, this study proposed a self-cascade strategy for activating and amplifying the cgas-sting pathway with specificity mediated by pyroptosis, representing a valuable avenue for future cancer catalytic metalloimmunotherapy. |
影响因子： | 14.4 |
分区情况： | 一区 |
链接： | 责任编辑：杜欣 |
