Bacteria-nanomaterial co-delivery systems for precision therapy: interfacial design, transport behavior, and translational barriers

Bacterial delivery systems, including validated probiotic strains and other attenuated or engineered bacterial carriers, have emerged as promising platforms for site-specific therapy. Viable cells can sense microenvironments, migrate actively, and generate biological outputs in situ. Clinical translation is nevertheless constrained by poor survival during gastrointestinal transit and rapid immune clearance. Target accumulation can also be variable, and cargo retention and release are often insufficiently controlled. Interfacial engineering with nanomaterials can address these limitations by protecting cells during transport and regulating bacterial activity. It can also maintain bacteria–cargo co-localization and enable site-specific functional exposure. This review focuses primarily on viable intact bacteria. Non-viable intact cells or bacterial ghosts are included only when the preserved whole-cell architecture provides a defined delivery function. We establish a framework that links co-delivery architecture and route-specific barriers with quantitative evaluation, cargo–bacteria interactions, in vivo transport, and translational performance. We emphasize two groups of trade-offs: interfacial stability versus bacterial activity, and targeting specificity versus release kinetics. Formulation reproducibility, quality control, and safety are also considered.Methods A literature search was conducted using ProQuest and PubMed, covering publications from August 2016 to August 2026. Older references were included as appropriate.