Engineered Bacteria-Nano Hybrid System: The Intelligent Drug Factory for Next-Generation Cancer Immunotherapy.

As one of the primary fatal diseases globally, cancer represents a severe threat to human health because of its high incidence and fatality rates. While traditional treatments including surgery, radiation, and conventional pharmacotherapy demonstrate therapeutic effects, they commonly suffer from issues like severe side effects, high rates of relapse, and immunosuppression. The advent of immune checkpoint inhibitors and targeted drugs has undoubtedly revolutionized cancer management and improved survival; however, a significant proportion of patients still encounter obstacles such as acquired resistance, an immunosuppressive tumor microenvironment, and poor drug delivery to avascular tumor regions. Recent integration of engineered bacteria with nanomaterials has offered novel strategies for cancer immunotherapy. Engineered bacteria feature natural tumor tropism, immune-stimulating properties, and programmability, while nanomaterials are characterized by high drug payload, tunable release profiles, and versatile functionality. This article reviews the application of hybrid systems integrating engineered bacteria and nanomaterials in cancer immunotherapy, exploring their potential for drug delivery, immunomodulation, targeted treatment, and smart responsiveness. The construction of an "intelligent drug factory" through the merger of bacterial biological traits and sophisticated nanomaterial functions enables precise manipulation of the tumor microenvironment and potent immune activation, thereby establishing a novel paradigm for the precise treatment of solid tumors. However, its clinical translation faces challenges such as long-term biosafety, genetic stability, and precise spatiotemporal control. Synergistic integration with therapies such as radiotherapy, chemotherapy, and immunotherapy represents a promising direction worthy of exploration.