Engineered nano-bacteria hybrids for precision cancer immunotherapy

Bacterial therapy has emerged as a promising modality in precision cancer immunotherapy, leveraging bacteria's innate tumor-homing ability, immunostimulatory properties, and engineering flexibility to overcome limitations in conventional treatments. This review highlights recent advances in integrating nanotechnology with bacterial systems to develop multifunctional platforms for precision cancer immunotherapy. We first discuss the development of nano-bacteria hybrids, including physical, chemical, and biological interface strategies for constructing multifunctional hybrids, as well as the therapeutic utility of bacterial-derived components such as outer membrane vesicles (OMVs), bacterial ghosts (BGs), and gas vesicles (GVs). We then discuss the synergistic integration of nano-bacteria hybrids with immune checkpoint blockade, CAR-T cell therapy, and genetic engineering approaches to enhance drug delivery, modulate the tumor microenvironment (TME), and improve immune activation. Finally, we explore innovative strategies to overcome current limitations in bacterial immunotherapy, such as tumor heterogeneity, immunosuppression, and safety concerns, while proposing future directions for the clinical translation of nano-bacteria hybrids.