Engineering 2D Multienzyme-Mimicking Pyroptosis Inducers for Ultrasound-Augmented Catalytic Tumor Nanotherapy
Xinran Song1, Hui Huang1, Lili Xia1
1School of Environmental and Chemical Engineering, Shanghai University, Shanghai, 200444, P. R. China.
Abstract:
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.
Insights
Engineered 2D NiCoOx nanosheets induce cancer cell death via pyroptosis by generating reactive oxygen species (ROS). Ultrasound enhances this effect, offering a novel nanotherapy approach for cancer treatment.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapy
Background:
- Apoptosis resistance hinders effective cancer treatment.
- Targeted pyroptosis offers a promising alternative cell death pathway.
- Limited efficient pyroptosis inducers exist for cancer therapy.
Purpose of the Study:
- To engineer 2D NiCoOx nanosheets as pyroptosis inducers for cancer therapy.
- To investigate their application in ultrasound-augmented catalytic tumor nanotherapy.
- To explore their multienzyme-mimicking activities for reactive oxygen species (ROS) production.
Main Methods:
- Fabrication of 2D NiCoOx nanosheets with peroxidase-, oxidase-, glutathione peroxidase-, and catalase-mimicking activities.
- Application in a ROS-induced pyroptosis pathway (ROS-NLRP3-GSDMD).
- Ultrasound (US) augmentation to enhance catalytic activities and ROS generation.
Main Results:
- NiCoOx nanosheets reversed hypoxia, depleted glutathione, and produced continuous ROS.
- Ultrasound activation amplified ROS generation and induced mitochondrial dysfunction.
- Experimental results confirmed NiCoOx-induced pyroptosis as the dominant anti-cancer mechanism.
Conclusions:
- Engineered 2D NiCoOx nanosheets effectively induce pyroptosis for cancer therapy.
- US-augmented nanotherapy shows promise for breast cancer treatment.
- The study enhances understanding of nanomaterial multienzyme activities in biomedical applications.
