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A Self-Priming Pyroptosis-Inducing Agent for Activating Anticancer Immunity.

Yanjie Li^1,2,3,4,5,6, Hanxin Feng^1,2,3,4,5,6, Huang Yang^1,7

¹Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China.

Advanced Healthcare Materials

|March 12, 2025

Summary

This study introduces MnNZ@OMV, a novel agent that effectively triggers pyroptosis in tumor cells. This approach enhances anti-tumor immunity by activating immune cells and promoting cancer immunotherapy.

Keywords:

anticancer immunity nanoenzyme outer membrane vesicles pyroptosis

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Area of Science:

Biotechnology
Immunology
Materials Science

Background:

Pyroptosis, a programmed cell death pathway, is a promising strategy for anti-tumor immunity.
Challenges exist in efficiently inducing pyroptosis in tumor cells due to limited caspase activation.

Purpose of the Study:

To develop a self-priming pyroptosis-inducing agent (MnNZ@OMV) for enhanced anti-tumor immunity.
To investigate the mechanism of MnNZ@OMV-induced pyroptosis via the noncanonical caspase-11/GSDMD pathway.

Main Methods:

Integration of outer membrane vesicles (OMVs) with manganese dioxide nanozymes (MnNZ) to create MnNZ@OMV.
In vitro and in vivo studies to assess MnNZ@OMV's ability to induce pyroptosis, deplete glutathione, generate reactive oxygen species, and activate immune cells.

Main Results:

MnNZ@OMV effectively induces pyroptosis in tumor cells by responding to intracellular glutathione (GSH).
The agent triggers NF-κB translocation, primes caspase-11 expression, and leads to GSDMD cleavage.
In vivo studies demonstrated MnNZ@OMV's ability to promote dendritic cell maturation and CD8+ T cell activation, resulting in significant anti-tumor effects.

Conclusions:

A novel self-priming pyroptosis-inducing agent (MnNZ@OMV) was successfully developed.
This approach utilizes the noncanonical caspase-11/GSDMD pathway for tumor cell pyroptosis induction.
MnNZ@OMV shows significant potential as a therapeutic strategy for cancer immunotherapy.