Abstract
Current clinical cancer treatments primarily rely on surgery, chemotherapy, radiotherapy, and immunotherapy; however, each approach has inherent limitations. In recent years, nanomaterials have gained significant attention in oncology due to their advantages in precise drug delivery, enhanced targeting, and improved therapeutic efficacy. Nevertheless, their clinical application remains limited by challenges such as complex synthesis, high costs, low delivery efficiency, and poor biodegradability. Bifidobacterium (BBM), a clinically used probiotic, has demonstrated unique tumor-targeting potential due to its obligate anaerobic nature, allowing it to selectively colonize, proliferate, and expand within the hypoxic tumor microenvironment. Recent advancements in synthetic biology and bacterial engineering have enabled the modification of Bifidobacterium as a microrobot for molecular imaging, drug or gene delivery, and other therapeutic functions. Compared to nanomaterials, Bifidobacterium-based bacterial therapy holds promise in overcoming certain limitations while potentially enhancing comprehensive cancer treatment by modulating the tumor microenvironment and boosting host immune responses. This review summarizes the latest progress in Bifidobacterium-mediated tumor imaging and therapy, explores its mechanisms of action, engineering strategies, and clinical applications, and discusses future directions for optimizing its functional design to improve therapeutic efficacy and safety.