Oral artificial microbio-vaccine triggers synergistic immunogenic cell death induction and tumor microenvironment remodeling for liver cancer therapy.
5 affiliations
- 1Chinese Medicine Germplasm Resources Innovation and Effective Uses Key Laboratory of Sichuan Province, Chengdu University of Traditional Chinese Medicine, Chengdu 611130, China.
- 2Department of Rehabilitation Sciences, Faculty of Health and Social Sciences, Hong Kong Polytechnic University Hong Kong 999077, China.
- 3School of Preclinical Medicine, Chengdu University, Chengdu 610106, China.
- 4Department of Urology, Peking University Third Hospital, Beijing 100191, China.
- 5TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China.
Abstract
Artificial cellular systems, engineered to mimic biological functions, offer a promising platform for advanced drug delivery and immunotherapy. Translating such systems into effective oral tumor vaccines, however, remains challenging due to the harsh gastrointestinal environment, inefficient immune activation, and the toxicity of potent immunogenic agents. To overcome these barriers, we engineered an oral artificial micro bio-vaccine via a hierarchical assembly strategy. Triptolide (TP), an immunogenic cell death inducer, was co-assembled with glycyrrhizic acid (GA), an immunomodulator, into a nanodetoxifying core to facilitate efficient loading into hollow Saccharomyces cerevisiae microcapsules (YC), forming the final aggregate (TP/GA-NYPs). This rational design leverages the YC for gastric protection and gut mucosa-targeting, while the Chitosan shell ensures robust encapsulation. Crucially, the TP/GA core demonstrates a synergistic interplay, in which TP potently induces immunogenic cell death, while GA concurrently remodels the immunosuppressive tumor microenvironment by suppressing metastasis-related markers and enhancing immunostimulatory cytokine profiles. This spatiotemporally coupled action within a single oral aggregate elicits robust intestinal mucosal and systemic immunity, effectively suppressing liver cancer progression and metastasis while mitigating the systemic toxicity of TP. This work highlights the therapeutic potential of functional aggregates in orchestrating synergistic anti-tumor immunity and offers a versatile platform for oral immunotherapy.
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BibTeX
@article{cheng2026oral,
title = {{Oral artificial microbio-vaccine triggers synergistic immunogenic cell death induction and tumor microenvironment remodeling for liver cancer therapy.}},
author = {Qian Cheng and Siyao Li and Lu Deng and Li Xiong and Huiling Hu and Jingjing Li and Lele Zhang and Boda Guo and Chuan Zheng and Jinming Zhang},
journal = {Acta pharmaceutica Sinica. B},
year = {2026},
month = jul,
doi = {10.1016/j.apsb.2026.06.058},
url = {https://europepmc.org/article/MED/42948444},
note = {CC BY},
}
RIS
TY - JOUR
TI - Oral artificial microbio-vaccine triggers synergistic immunogenic cell death induction and tumor microenvironment remodeling for liver cancer therapy.
AU - Qian Cheng
AU - Siyao Li
AU - Lu Deng
AU - Li Xiong
AU - Huiling Hu
AU - Jingjing Li
AU - Lele Zhang
AU - Boda Guo
AU - Chuan Zheng
AU - Jinming Zhang
PY - 2026
DA - 2026/07/04
JO - Acta pharmaceutica Sinica. B
DO - 10.1016/j.apsb.2026.06.058
UR - https://europepmc.org/article/MED/42948444
AB - Artificial cellular systems, engineered to mimic biological functions, offer a promising platform for advanced drug delivery and immunotherapy. Translating such systems into effective oral tumor vaccines, however, remains challenging due to the harsh gastrointestinal environment, inefficient immune activation, and the toxicity of potent immunogenic agents. To overcome these barriers, we engineered an oral artificial micro bio-vaccine via a hierarchical assembly strategy. Triptolide (TP), an immunogenic cell death inducer, was co-assembled with glycyrrhizic acid (GA), an immunomodulator, into a nanodetoxifying core to facilitate efficient loading into hollow Saccharomyces cerevisiae microcapsules (YC), forming the final aggregate (TP/GA-NYPs). This rational design leverages the YC for gastric protection and gut mucosa-targeting, while the Chitosan shell ensures robust encapsulation. Crucially, the TP/GA core demonstrates a synergistic interplay, in which TP potently induces immunogenic cell death, while GA concurrently remodels the immunosuppressive tumor microenvironment by suppressing metastasis-related markers and enhancing immunostimulatory cytokine profiles. This spatiotemporally coupled action within a single oral aggregate elicits robust intestinal mucosal and systemic immunity, effectively suppressing liver cancer progression and metastasis while mitigating the systemic toxicity of TP. This work highlights the therapeutic potential of functional aggregates in orchestrating synergistic anti-tumor immunity and offers a versatile platform for oral immunotherapy.
SN - 2211-3835
SN - 2211-3843
ER -