Engineered bacteria for antitumor drug delivery

Abstract

Bacteria have emerged as a promising platforms for drug delivery in recent years due to their unique biological properties. Compared with conventional delivery systems, bacterial carriers offer distinct advantages, including the ability of obligate and facultative anaerobes to selectively colonize tumor tissues. Their inherent motility allows them to penetrate physical barriers within tumors and reach hypoxic regions that are typically inaccessible to traditional therapeutic agents. Moreover, their natural immunogenicity and interaction with the tumor microenvironment provide additional opportunities for cancer therapy. Through genetic engineering and synthetic biology, bacteria can also be programmed to express and deliver various therapeutic molecules, such as cytokines, antigens, and immune activators. Currently, attenuated strains of Salmonella , Listeria , and certain probiotic species are among the main bacterial vectors, retaining tumor-targeting capacity while exhibiting reduced pathogenicity and toxicity. In addition to live bacterial carriers, bacterial derivatives, including outer membrane vesicles, bacterial ghosts, minicells, and spores, have also attracted increasing attention as alternative delivery platforms. Loading and delivery strategies for bacterial carriers encompass genetic modification, surface engineering, physical adsorption, chemical coupling, secretion systems, and controlled bacterial lysis. Furthermore, the integration of bacterial carriers with functional nanomaterials and intelligent responsive systems has enabled more precise and controllable drug delivery in response to tumor-associated stimuli, such as hypoxia, pH, reactive oxygen species, light, and magnetic fields. These advances have expanded the applications of bacteria-based delivery systems in chemotherapy, immunotherapy, and combination therapies. This review comprehensively summarizes recent progress in bacterial-based drug delivery systems, with a focus on their advantages, classifications, therapeutic applications, loading strategies, and emerging innovations. Advances in synthetic biology and nanotechnology are further expanding the potential of bacterial carriers for precision medicine.