Metal-polyphenol "prison" attenuated bacterial outer membrane vesicle for chemodynamics promoted in situ tumor vaccines
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Updated: Jul 9, 2025
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Weidong Nie1, Anqi Jiang1, Xu Ou1
1School of Life Science, Beijing Institute of Technology, Beijing 100081, PR China.
Abstract:
As natural adjuvants, the bacterial outer membrane vesicles (OMV) hold great potential in cancer vaccines. However, the inherent immunotoxicity of OMV and the rarity of tumor-specific antigens seriously hamper the clinical translation of OMV-based cancer vaccines. Herein, metal-phenolic networks (MPNs) are used to attenuate the toxicity of OMV, meanwhile, provide tumor antigens via the chemodynamic effect induced immunogenic cell death (ICD). Specifically, MPNs are assembled on the OMV surface through the coordination reaction between ferric ions and tannic acid. The iron-based "prison" is locally collapsed in the tumor microenvironment (TME) with both low pH and high ATP features, and thus the systemic toxicity of OMV is significantly attenuated. The released ferric ions in TME promote the ICD of cancer cells through Fenton reaction and then the generation of abundant tumor antigens, which can be used to fabricate in-situ vaccines by converging with OMV. Together with the immunomodulatory effect of OMV, potent tumor repression on a bilateral tumor model is achieved with good biosafety.
Insights
Metal-phenolic networks (MPNs) reduce the toxicity of bacterial outer membrane vesicles (OMVs) for cancer vaccines. MPNs also generate tumor antigens via immunogenic cell death, enhancing vaccine efficacy and safety.
Area of Science:
- Biotechnology
- Nanotechnology
- Immunology
Background:
- Bacterial outer membrane vesicles (OMVs) show promise as cancer vaccine adjuvants.
- OMV immunotoxicity and lack of tumor-specific antigens limit their clinical use.
- Metal-phenolic networks (MPNs) offer a strategy to overcome these limitations.
Purpose of the Study:
- To develop a novel OMV-based cancer vaccine using MPNs to attenuate toxicity and provide tumor antigens.
- To investigate the mechanism of MPN-induced immunogenic cell death (ICD) in the tumor microenvironment (TME).
- To evaluate the therapeutic efficacy and biosafety of the developed vaccine in a preclinical model.
Main Methods:
- MPNs were assembled on OMV surfaces using ferric ions and tannic acid.
- The MPN-OMV system was designed to release iron in the TME (low pH, high ATP).
- Chemodynamic therapy via Fenton reaction induced ICD and released tumor antigens for in-situ vaccination.
Main Results:
- MPN coating significantly attenuated OMV systemic toxicity.
- The MPN-OMV system effectively induced ICD and generated tumor antigens in the TME.
- Combined OMV immunomodulation and MPN-derived antigens led to potent tumor repression in a bilateral tumor model.
- The vaccine demonstrated good biosafety.
Conclusions:
- MPN-coated OMVs represent a promising strategy for developing safer and more effective cancer vaccines.
- This approach leverages MPNs to enhance tumor antigen presentation and reduce OMV-related toxicity.
- The developed in-situ vaccine demonstrates significant therapeutic potential with favorable safety.
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