Engineering versatile nano-bacteria hybrids for efficient tumor therapy

With the remarkable advances of bacteriotherapy and diverse functional nanoplatforms in biomedical applications, nano-bacteria hybrids have been extensively exploited as the emerging and distinct theranostic platforms and strategies for enhanced tumor therapy. The nano-bacteria hybrids are highly competent for efficient anticancer therapy when combined the hypoxia tropism and chemotaxis, penetration capabilities, extracellular anticancer metabolites, immunogenic effects and specific respiration of specialty bacteria with the tunable physicochemical properties, easily modified surface, multifunctionality of versatile nanoparticles together. Herein, efforts are made to provide a comprehensive review on the current progress of anticancer nano-bacteria hybrid systems, ranging from the promising types of live bacteria such as obligate anaerobe Cyanobacteria and facultative anaerobe Salmonella, rational fabrication methods including covalent bond, physical adsorption, biomineralization process, and other binding forms, to their versatile applications in several distinct therapeutic modalities including drug delivery, immunotherapy, phototherapy, chemodynamic therapy, sonodynamic therapy, gas therapy, pyroptosis and bio-imaging in efficient cancer treatment. The biosafety evaluation, unsettled challenges, and future perspectives on the rational construction of nano-bacteria hybrids and their further clinical translations have also been discussed and outlooked. It is highly anticipated that the unique theranostic platforms of nano-bacteria hybrids will witness a leap-forward development in clinical translation for precise and personalized cancer therapy.