机构：[1]Tea Resources Utilization and Quality Testing Key Laboratory of Sichuan Province, College of Horticulture, Sichuan Agricultural University, Chengdu, Sichuan 611130, China.[2]BMI Center for Biomass Materials and Nanointerfaces, National Engineering Laboratory for Clean Technology of Leather Manufacture, Ministry of Education Key Laboratory of Leather Chemistry and Engineering, College of Biomass Science and Engineering, Sichuan University, Chengdu, Sichuan 610065, China.[3]Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Yuzhong, Chongqing 400016, China.重庆医科大学附属第一医院[4]State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China.[5]State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu, Sichuan 610065, China.[6]Bioproducts Institute, Department of Chemical and Biological Engineering, The University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada.
The immuno-oncology-microbiome (IOM) axis, referring to the gut microbiota-regulated immune interactions on the tumor microenvironment and systemic immunity, is essential for cancer therapies. However, the cytotoxicity of chemotherapeutic agents (Chemos) disrupts the gut microbiota- and gut microbiota-manipulated IOM axis, further diminishing the therapeutic efficacy. Here, we developed oral nanoarmored live bacterial biotherapeutics (supraLBT), to reshape the tumor microenvironment and enhance chemotherapy via reestablishing the IOM axis. The cyto-adhesive polyphenol-based supraparticles, made from green tea polyphenol and food-grade milk protein, attached on microbes (Escherichia coli Nissle1917, EcN) resisted a range of clinically relevant Chemos via phenolic-mediated noncovalent interactions, enhancing supraLBT survival by 27-fold compared with bare EcN. SupraLBT restored the intestinal microbiota and the disrupted IOM axis, thereby reducing the infiltration of regulatory T cells, increasing the recruitment of cytotoxic CD8+ T cells to the tumor bed, and further inhibiting tumor proliferation and demonstrating enhanced systemic immune responses. Notably, oral supraLBT combined with chemotherapy (doxorubicin) exhibited 2.35-fold greater tumor regression than that of doxorubicin alone, indicating that oral supraLBT can enhance the chemotherapeutic effect. Further investigations revealed that supraLBT reprogrammed the immune tumor microenvironment by upregulating antitumor cytokines and altering the gut microbial composition. Given the intricate interplay between gut microbiota, host immune system, and tumor microenvironment, this work presents a facile and biomaterial-engineered microorganism-based strategy to enhance the synergistic immuno-chemotherapy effects.
基金：
The authors
acknowledge financial support from the National Key R&D
Program of China (2022YFA0912800), the National Excellent
Young Scientists Fund (00308054A1045), the National
Natural Science Foundation of China (22178233), the Talents
Program of Sichuan Province, the Double First-Class
University Plan of Sichuan University, the State Key
Laboratory of Polymer Materials Engineering (sklpme 2020-
03-01), Science and Technology Project of Sichuan Province
(2020YFN0154), the Tianfu Emei Program of Sichuan
Province (2022-EC02-00073-CG), the Postdoctoral special
funding of Sichuan Province (TB2022063), the Postdoctoral
Funding of Sichuan University (2022SCU12099), Fundamental
Research Funds for the Central Universities
(SCU2025D014), the Chongqing Graduate Research Innovation
Project (CYB23197), the First-class Discipline Construction
Project of the First Affiliated Hospital of Chongqing
Medical University (CYYY-BSYJSCXXM-202304), and Ministry
of Education Key Laboratory of Leather Chemistry and
Engineering.
第一作者机构：[1]Tea Resources Utilization and Quality Testing Key Laboratory of Sichuan Province, College of Horticulture, Sichuan Agricultural University, Chengdu, Sichuan 611130, China.[2]BMI Center for Biomass Materials and Nanointerfaces, National Engineering Laboratory for Clean Technology of Leather Manufacture, Ministry of Education Key Laboratory of Leather Chemistry and Engineering, College of Biomass Science and Engineering, Sichuan University, Chengdu, Sichuan 610065, China.
通讯作者：
通讯机构：[2]BMI Center for Biomass Materials and Nanointerfaces, National Engineering Laboratory for Clean Technology of Leather Manufacture, Ministry of Education Key Laboratory of Leather Chemistry and Engineering, College of Biomass Science and Engineering, Sichuan University, Chengdu, Sichuan 610065, China.[5]State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu, Sichuan 610065, China.[6]Bioproducts Institute, Department of Chemical and Biological Engineering, The University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada.
推荐引用方式(GB/T 7714)：
Liu Qinling,Wu Yue,Fan Qingxin,et al.Oral Nanoarmored Live Bacterial Biotherapeutics Bearing Polyphenol-Based Supraparticles Enhance Chemotherapy via Reestablishing Immuno-Oncology-Microbiome Axis[J].ACS Nano.2025,19(26):23575-23591.doi:10.1021/acsnano.5c01158.
APA：
Liu Qinling,Wu Yue,Fan Qingxin,Liu Jialing,Chen Yan...&Guo Junling.(2025).Oral Nanoarmored Live Bacterial Biotherapeutics Bearing Polyphenol-Based Supraparticles Enhance Chemotherapy via Reestablishing Immuno-Oncology-Microbiome Axis.ACS Nano,19,(26)
MLA：
Liu Qinling,et al."Oral Nanoarmored Live Bacterial Biotherapeutics Bearing Polyphenol-Based Supraparticles Enhance Chemotherapy via Reestablishing Immuno-Oncology-Microbiome Axis".ACS Nano 19..26(2025):23575-23591
材料科学