Bacterially mediated drug delivery and therapeutics: Strategies and advancements

It was already clinically apparent 150 years ago that bacterial therapy could alleviate diseases. Recently, a burgeoning number of researchers have been using bacterial regimens filled with microbial therapeutic leads to diagnose and treat a wide range of disorders and diseases, including cancers, inflammatory diseases, metabolic disorders and viral infections. Some bacteria that were designed to have low toxicity and high efficiency in drug delivery have been used to treat diseases successfully, especially in tumor therapy in animal models or clinical trials, thanks to the progress of genetic engineering and synthetic bioengineering. Therefore, genetically engineered bacteria can serve as efficient drug delivery vehicles, carrying nucleic acids or genetic circuits that encode and regulate therapeutic payloads. In this review, we summarize the development and applications of this approach. Strategies for genetically modifying strains are described in detail, along with their objectives. We also describe some controlled strategies for drug delivery and release using these modified strains as carriers. Furthermore, we discuss treatment methods for various types of diseases using engineered bacteria. Tumors are discussed as the most representative example, and other diseases are also briefly described. Finally, we discuss the challenges and prospects of drug delivery systems based on these bacteria.