Engineered bacterium-nanomedicine complexes in cancer therapy: Designs, applications and challenges

In recent years, nanomedicines have shown extensive potential applications in tumor therapy, which, however, still suffer from various drawbacks such as unsatisfactory targeting efficiency, insufficient tumor penetration, and serious side effects, leading to the greatly limited therapeutic effectiveness of tumors and impeded development of nanocatalytic medicine. In contrast, engineered bacteria and their secretions exhibit promising characteristics of selectively targeting the tumor microenvironments and stimulating robust immune responses. Nonetheless, as a new type of treatment, bacterium-based therapeutics still faces critical issues such as bio-safety and suboptimal efficacies. Nowadays, an increasing number of studies have confirmed that the combination between nanomedicines and engineered bacteria can perfectly highlight the advantages of both approaches, and furthermore, present the synergistic potentials between them based on their respective strengths, thus providing great possibilities for future cancer treatments. In order to promote the advance of this research field, we review the most recent progresses in the field by introducing various types of complexes between engineered bacteria or their metabolites and nanomedicines, as well as the synergetic mechanisms of actions in tumor therapy. Additionally, the key issues in the existing field and their future prospects are discussed and prospected to further aid the development of this field.