DataVXAdvanced MaterialsPaper
journal article·2024-02

Engineering Clinically Relevant Probiotics with Switchable “Nano‐Promoter” and “Nano‐Effector” for Precision Tumor Therapy

Fangfang Cao, Lulu Jin, Chenyin Zhang, Yong Gao, Zhefeng Qian, Hongyang Wen, Sisi Yang, Ziqiang Ye, Liangjie Hong, Huang Yang, Zongrui Tong, Liang Cheng, Yuan Ding, Weilin Wang, Guocan Yu, Zhengwei Mao, Xiaoyuan Chen

Advanced Materials· Volume 36· Issue 5
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Source abstract

Abstract

Abstract Probiotics have the potential as biotherapeutic agents for cancer management in preclinical models and human trials by secreting antineoplastic or immunoregulatory agents in the tumor microenvironment (TME). However, current probiotics lack the ability to dynamically respond to unique TME characteristics, leading to limited therapeutic accuracy and efficacy. Although progress has been made in customizing controllable probiotics through synthetic biology, the engineering process is complex and the predictability of production is relatively low. To address this, here, for the first time, this work adopts pH‐dependent peroxidase‐like (POD‐like) artificial enzymes as both an inducible “nano‐promoter” and “nano‐effector” to engineer clinically relevant probiotics to achieve switchable control of probiotic therapy. The nanozyme initially serves as an inducible “nano‐promoter,” generating trace amounts of nonlethal reactive oxygen species (ROS) stress to upregulate acidic metabolites in probiotics. Once metabolites acidify the TME to a threshold, the nanozyme switches to a “nano‐effector,” producing a great deal of lethal ROS to fight cancer. This approach shows promise in subcutaneous, orthotopic, and colitis‐associated colorectal cancer tumors, offering a new methodology for modulating probiotic metabolism in a pathological environment.
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Research context

Nanomaterials

OpenAlex topics: Nanoplatforms for cancer theranostics · Advanced Nanomaterials in Catalysis · Cancer Research and Treatments

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Departments of Diagnostic Radiology Surgery Chemical and Biomolecular Engineering and Biomedical Engineering Yong Loo Lin School of Medicine and College of Design and Engineering National University of Singapore Singapore 119074 Singapore

Nanomedicine Translational Research Program NUS Center for Nanomedicine Yong Loo Lin School of Medicine National University of Singapore Singapore 117597 Singapore

MOE Key Laboratory of Macromolecular Synthesis and Functionalization Department of Polymer Science and Engineering Zhejiang University Hangzhou 310027 China

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

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious Diseases National Medical Center for Infectious Diseases Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases The First Affiliated Hospital School of Medicine Zhejiang University Hangzhou 310003 China

Institute of Functional Nano & Soft Materials (FUNSOM) Jiangsu Key Laboratory for Carbon Based Functional Materials & Devices Soochow University Suzhou 215123 China

Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology Department of Chemistry Tsinghua University Beijing 100084 China

Clinical Imaging Research Centre Centre for Translational Medicine Yong Loo Lin School of Medicine National University of Singapore Singapore 117599 Singapore

Institute of Molecular and Cell Biology Agency for Science Technology, and Research (A*STAR) 61 Biopolis Drive, Proteos Singapore 138673 Singapore

Funding

National Natural Science Foundation of China · Science and Technology Department of Zhejiang Province · National University of Singapore · National Medical Research Council · National Research Foundation

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