Engineering 2D Multienzyme-Mimicking Pyroptosis Inducers for Ultrasound-Augmented Catalytic Tumor Nanotherapy

被引:21
|
作者
Song, Xinran [1 ]
Huang, Hui [1 ]
Xia, Lili [1 ]
Jia, Wencong [1 ]
Yang, Shaoling [2 ]
Wang, Chenglong [3 ]
Chen, Yu [1 ]
机构
[1] Shanghai Univ, Sch Environm & Chem Engn, Shanghai 200444, Peoples R China
[2] Shanghai Eighth Peoples Hosp, Dept Ultrasound Med, Shanghai 200235, Peoples R China
[3] Shanghai Jiao Tong Univ, XinHua Hosp Affiliated, Dept Orthoped Surg, Sch Med, Shanghai 200082, Peoples R China
基金
中国国家自然科学基金;
关键词
2D nanosheets; catalytic therapy; multienzyme-mimicking; pyroptosis; ultrasound therapy; NANOZYME; GSDMD; MECHANISM; CASPASES; ALBUMIN;
D O I
10.1002/advs.202301279
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Overcoming apoptosis resistance is necessary to ensure an effective cancer treatment; however, it is currently very difficult to achieve. A desirable alternative for cancer treatment is the targeted activation of pyroptosis, a unique type of programmed cell death. However, the pyroptosis inducers that are efficient for cancer therapy are limited. This work reports the engineering of 2D NiCoOx nanosheets as inducers of the production of harmful reactive oxygen species (ROS), which promote intense cell pyroptosis, and that can be applied to ultrasound (US)-augmented catalytic tumor nanotherapy. The main therapeutic task is carried out by the 2D NiCoOx nanosheets, which have four multienzyme-mimicking activities: peroxidase- (POD), oxidase- (OXD), glutathione peroxidase- (GPx), and catalase- (CAT) mimicking activities. These activities induce the reversal of the hypoxic microenvironment, endogenous glutathione depletion, and a continuous ROS output. The ROS-induced pyroptosis process is carried out via the ROS-NLRP3-GSDMD pathway, and the exogenous US activation boosts the multienzyme-mimicking activities and favors the incremental ROS generation, thus inducing mitochondrial dysfunction. The anti-cancer experimental results support the dominance of NiCoOx nanosheet-induced pyroptosis. This work expands on the biomedical applications of engineering 2D materials for US-augmented catalytic breast cancer nanotherapy and deepens the understanding of the multienzyme activities of nanomaterials.
引用
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页数:13
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