A Microrobotic System Based on Engineered Bacteria for Targeted Self‐Driven Photodynamic Therapy

Photodynamic therapy (PDT) has been used clinically to treat superficial tumors for decades. However, its effectiveness against deep-seated tumors has been limited by the inefficient delivery of the key components -light, photosensitizer, and oxygen- required for the photochemical reactions in PDT. Here, we present a novel platform that enables the photochemical reaction to occur in a self-driven manner, eliminating the need for external delivery of these components and instead orchestrating their endogenous generation within tumors. This was achieved by genetically modifying probiotic Escherichia coli to host three modules - Lux, Hem1, and KatG - responsible for light production, photosensitizer biosynthesis, and oxygen generation, respectively. The system is self-driven, relying solely on substrates within E. coli cells and tumors. The modules exhibited prolonged activity for days within in vivo mouse models, enabling metronomic PDT that induced an immune response. This research holds promise for revolutionizing PDT and overcoming the enduring challenges encountered in its application for treating deep-seated tumors.