"Multi-in-One" Yolk-Shell Structured Nanoplatform Inducing Pyroptosis and Antitumor Immune Response Through Cascade...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapy

Background:

• Pyroptosis, a regulated cell death pathway, shows promise in cancer treatment by activating antitumor immune responses.
• Elevating intracellular reactive oxygen species (ROS) is a key strategy to induce pyroptosis.
• The tumor microenvironment (TME) often presents challenges for effective cancer therapy.

Purpose of the Study:

• To construct an integrated nanoplatform (hCZAG) for inducing pyroptosis and enhancing antitumor immunity.
• To investigate the role of glucose oxidase (GOx) and metal ions (Cu2+, Zn2+) in triggering cell death pathways.
• To explore the potential of hCZAG in cancer immunotherapy.

Main Methods:

• Fabrication of a zeolitic imidazolate framework-8 (ZIF-8) based nanoplatform (hCZAG) loaded with glucose oxidase (GOx).
• Utilizing Cu2+ and Zn2+ as active nodes within the nanoplatform to promote ROS generation and oxidative stress.
• Investigating the induction of pyroptosis via ROS outburst, Caspase-1 activation, and GSDMD cleavage, alongside cuproptosis induction.

Main Results:

• The hCZAG nanoplatform effectively increased intracellular H2O2 levels, modulating the TME.
• Cu2+ ions promoted ROS generation and amplified oxidative stress, while also inducing cuproptosis.
• The generated ROS triggered pyroptosis, leading to immunogenic cell death (ICD) and activating adaptive immune responses.

Conclusions:

• The hCZAG nanoplatform is a viable strategy for inducing pyroptosis and cuproptosis, offering a dual-pronged approach to cancer cell death.
• This approach effectively elicits an antitumor immune response, paving the way for enhanced cancer immunotherapy.
• The study highlights the potential of integrated nanoplatforms in advancing pyroptosis-mediated cancer treatment.