Innovative Applications of Bacteria and Their Derivatives in Targeted Tumor Therapy.

Despite significant progress in cancer treatment, traditional therapies still face considerable challenges, including poor targeting, severe toxic side effects, and the development of resistance. Recent advances in biotechnology have revealed the potential of bacteria and their derivatives as drug delivery systems for tumor therapy by leveraging their biological properties. Engineered bacteria, including , , and , along with their derivatives─outer membrane vesicles (OMVs), bacterial ghosts (BGs), and bacterial spores (BSPs)─can be loaded with a variety of antitumor agents, enabling precise targeting and sustained drug release within the tumor microenvironment (TME). These bacteria and their derivatives possess intrinsic properties that stimulate the immune system, enhancing both innate and adaptive immune responses to further amplify therapeutic effects. The ability of bacteria to naturally accumulate in hypoxic tumor regions and their versatility in genetic modifications allow for tailored drug delivery strategies that synergistically enhance the effectiveness of chemotherapy, immunotherapy, and targeted therapies. This review comprehensively examines the fundamental principles of bacterial therapy, focusing on the strategies employed for bacterial engineering, drug loading, and the use of bacteria and their derivatives in targeted tumor therapy. It also discusses the challenges faced in optimizing bacterial delivery systems, such as safety concerns, unintended immune responses, and scalability for clinical applications. By exploring these aspects, this review provides a theoretical framework for improving bacterial-based drug delivery systems, contributing to the development of more effective and personalized cancer treatments.