Engineering Bacteria and Bionic Bacterial Derivatives with Nanoparticles for Cancer Therapy

Abstract Natural bacteria are interesting subjects for cancer treatments owing to their unique autonomy‐driven and hypoxic target properties. Genetically modified bacteria (such as bacteria with msbB gene and aroA gene modifications) can effectively cross sophisticated physiological barriers and transport antitumor agents into deep tumor tissues, and they have good biosafety. Additionally, bacteria can secrete cytokines (such as interleukin‐224, interferon‐gamma [IFN‐γ], and interleukin‐1β) and activate antitumor immune responses in the tumor microenvironment, resulting in tumor inhibition. All of these characteristics can be easily utilized to develop synergistic antitumor strategies by combining bacteria‐based agents with other therapeutic approaches. Herein, representative studies of bacteria‐instructed multimodal synergistic cancer therapy are introduced (e.g., photothermal therapy, chemoimmunotherapy, photodynamic therapy, and photocontrolled bacterial metabolite therapy), and their key advantages are systematically expounded. The current challenges and future prospects in advancing the development of bacteria‐based micro/nanomedicines in the field of synthetic biology research are also emphasized, which will hopefully promote the development of related bacteria‐based cancer therapies.