Targeted cancer therapy has brought new clinical approaches to the forefront, including the use of antibodies, small molecules, anti-angiogenics, and antivirals. However, these strategies are limited by the challenges of tumor accumulation and penetration.
Recently, synthetic biology has revitalized the idea of using living organisms to fight cancer. For instance, some bacteria can naturally accumulate in tumors, and can be engineered to induce local cytotoxicity while remaining harmless to the host. Clinical trials have demonstrated the safety and tolerance of strains such as E. coli and S. typhimurium for cancer therapy. S. typhimurium was initially shown to combat tumors through the recruitment of the host immune system and competition with cancer cells for nutrients, and later through the engineered production of therapeutic cargo through simple genetic modifications.
Synthetic biology is now taking this approach a step further by using genetic circuits with sophisticated sensing and delivery capabilities to enable bacteria to self-regulate therapeutic cargo production in response to tumor-specific stimuli.
Despite these exciting advances, there are still challenges in engineering bacteria for tumor therapy, such as safety, robust colonisation via effective delivery of tolerable doses as well as improving penetration of tumors. To address these hurdles, we are working on developing controllable, living biohybrid microrobots based on bacteria. This involves using either magnetotactic bacteria, which naturally produce magnetic particles, or functionalizing non-magnetic bacteria with magnetic nanomaterials for wireless magnetic control. These biohybrid microrobots are equipped with drug-filled nanoliposomes and/or therapeutic genetic circuits and are controlled and tracked using custom-built magnetic instrumentation and algorithms. This approach represents a promising, controllable, and biologically-based therapeutic platform for cancer treatment.