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Updated: May 13, 2026
Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
Published on: June 13, 2014
A RIG-I targeting nanozyme induces PANoptosis for cancer immunotherapy
Shuohui Dong1, Ye Yuan2, Haolin Cao3
1Department of General Surgery, Qilu Hospital of Shandong University, Jinan, China.
Abstract:
The emerging concept of PANoptosis-a lytic cell death pathway integrating apoptosis, pyroptosis, and necroptosis-presents avenues for cancer immunotherapy, yet its therapeutic exploitation remains limited by undefined molecular sensors and induction strategies. Here, we report a tumor-targeting nanozyme, Hemin-His-Mn, that concurrently activates retinoic acid-inducible gene I-mediated PANoptosome assembly and catalyzes reactive oxygen species amplification to achieve precision PANoptosis induction. Mechanistically, Hemin-His-Mn binds to retinoic acid-inducible gene I and alleviates its autoinhibition, initiating PANoptosome formation through the orchestrated recruitment of cell death executioners, thereby identifying retinoic acid-inducible gene I as a master PANoptosis sensor. In parallel, Hemin-His-Mn exerts peroxidase-like activity to generate cytotoxic reactive oxygen species surges, facilitating complete execution of PANoptosis. This dual mechanism promotes potent immunogenicity by releasing damage-associated molecular patterns and enhancing antigen presentation, ultimately eliciting robust T cell-mediated antitumor immunity. In multiple male mouse preclinical models, Hemin-His-Mn reprograms the tumor immune microenvironment and synergizes with immune checkpoint inhibitors. Our study introduces a retinoic acid-inducible gene I-targeting nanotechnology platform that redefines strategies for PANoptosis induction, provides mechanistic insights into PANoptosome assembly, and offers a clinically translatable modality for enhancing cancer immunotherapy.
Insights
Researchers developed Hemin-His-Mn, a nanozyme that precisely induces PANoptosis (programmed cell death) by targeting retinoic acid-inducible gene I. This approach enhances cancer immunotherapy by boosting T cell responses and synergizing with existing treatments.
Area of Science:
- Biomedical Engineering
- Immunology
- Oncology
Background:
- PANoptosis, a cell death pathway integrating apoptosis, pyroptosis, and necroptosis, offers potential for cancer immunotherapy.
- Current limitations include undefined molecular sensors and induction strategies for PANoptosis.
Purpose of the Study:
- To develop a novel nanozyme, Hemin-His-Mn, for precise induction of PANoptosis.
- To elucidate the mechanism of Hemin-His-Mn in activating PANoptosis via retinoic acid-inducible gene I (RIG-I).
- To evaluate the therapeutic potential of Hemin-His-Mn in preclinical cancer models.
Main Methods:
- Development of a tumor-targeting nanozyme, Hemin-His-Mn.
- Investigation of Hemin-His-Mn's interaction with RIG-I to induce PANoptosome assembly.
- Assessment of Hemin-His-Mn's peroxidase-like activity for reactive oxygen species generation.
- Evaluation of Hemin-His-Mn's efficacy in preclinical mouse models, including combination therapy with immune checkpoint inhibitors.
Main Results:
- Hemin-His-Mn activates RIG-I, initiating PANoptosome formation and identifying RIG-I as a key PANoptosis sensor.
- The nanozyme generates cytotoxic reactive oxygen species, ensuring complete PANoptosis execution.
- Hemin-His-Mn treatment enhanced immunogenicity by releasing DAMPs and improving antigen presentation.
- In preclinical models, Hemin-His-Mn reprogrammed the tumor immune microenvironment and showed synergy with immune checkpoint inhibitors.
Conclusions:
- Hemin-His-Mn represents a nanotechnology platform for targeted PANoptosis induction.
- The study provides mechanistic insights into PANoptosis regulation by RIG-I.
- This approach offers a clinically translatable strategy for enhancing cancer immunotherapy.
