Engineered bacteria and bacteria-derived nanomaterials for cancer therapy: Mechanisms, designs and advances

Bacteria have emerged as powerful and versatile platforms for cancer therapy, leveraging their inherent tumor-targeting capabilities, adaptability to engineering, and ability to interact dynamically with the tumor microenvironment (TME). This review systematically introduces the multimodal mechanisms of action underlying bacteria-based cancer therapeutics, from direct tumor lysis to bacterial tropism and immune modulation in the TME. We summarize engineering strategies for bacteria-based cancer therapy through two principal approaches: biological engineering (genetic reprogramming and biofilm encapsulation) and physicochemical modification (chemical conjugation, physical interaction, and biomineralization coating). This discussion highlights the key applications of live bacteria, including facultative anaerobes (e.g., Salmonella typhimurium (S. typhimurium) and Escherichia coli (E. coli), obligate anaerobes (e.g., Clostridium), and probiotics (e.g., Bifidobacterium), for precision oncotherapy. In addition to whole-cell therapies, we introduce bacterial derivatives such as outer membrane vesicles (OMVs) and membrane-coated nanoparticles as complementary approaches. Finally, we discuss key translational challenges in bacteria-based cancer therapies, including strain optimization, immune-related adverse effects, and manufacturing scalability. This review consolidates current advances in bacterial cancer therapy, offering a design framework to optimize microbial therapeutics. By bridging engineering principles with clinical needs, it provides actionable insights for developing safer, more effective living medicines against cancers.