Genetically engineered bacteria: a new frontier in targeted drug delivery

Genetically engineered bacteria (GEB) have shown significant promise to revolutionize modern medicine. These engineered bacteria with unique properties such as enhanced targeting, versatility, biofilm disruption, reduced drug resistance, self-amplification capabilities, and biodegradability represent a highly promising approach for targeted drug delivery and cancer theranostics. This innovative approach involves modifying bacterial strains to function as drug carriers, capable of delivering therapeutic agents directly to specific cells or tissues. Unlike synthetic drug delivery systems, GEB are inherently biodegradable and can be naturally eliminated from the body, reducing potential long-term side effects or complications associated with residual foreign constituents. However, several pivotal challenges such as safety and controllability need to be addressed. Researchers have explored novel tactics to improve their capabilities and overcome existing challenges, including synthetic biology tools (e.g., clustered regularly interspaced short palindromic repeats (CRISPR) and bioinformatics-driven design), microbiome engineering, combination therapies, immune system interaction, and biocontainment strategies. Because of the remarkable advantages and tangible progress in this field, GEB may emerge as vital tools in personalized medicine, providing precise and controlled drug delivery for various diseases (especially cancer). In this context, future directions include the integration of nanotechnology with GEB, the focus on microbiota-targeted therapies, the incorporation of programmable behaviors, the enhancement in immunotherapy treatments, and the discovery of non-medical applications. In this way, careful ethical considerations and regulatory frameworks are necessary for developing GEB-based systems for targeted drug delivery. By addressing safety concerns, ensuring informed consent, promoting equitable access, understanding long-term effects, mitigating dual-use risks, and fostering public engagement, these engineered bacteria can be employed as promising delivery vehicles in bio- and nanomedicine. In this review, recent advances related to the application of GEB in targeted drug delivery and cancer therapy are discussed, covering crucial challenging issues and future perspectives.