Engineering a living therapeutic: calcium phosphate-mineralized phycocyanobilin-producing E. coli as a self-contained photodynamic system

The complex synthesis, purification, and delivery of photosensitizers remain major bottlenecks for clinical photodynamic therapy (PDT). Here, we develop PCB@Ecoli@CaP, an engineered Escherichia coli –based living therapeutic that autonomously biosynthesizes the natural photosensitizer phycocyanobilin (PCB) and is encapsulated within a calcium phosphate (CaP) shell to form a self-contained photodynamic system. Under 660 nm laser irradiation, PCB@Ecoli@CaP efficiently generates reactive oxygen species (ROS), which induce potent oxidative stress to eradicate 4T1 tumor cells and simultaneously trigger bacterial self-killing, thereby establishing a self-limiting therapeutic platform. The CaP coating enhances biocompatibility and stability while modulating light penetration and ROS release, as confirmed by DPBF photobleaching, intracellular ROS imaging, and CCK-8 viability measurements. This dual-function system integrates in situ photosensitizer biosynthesis, on-demand photodynamic activation, and built-in safety through self-elimination into a single, programmable microbial platform, offering a simplified, scalable, and safer strategy for next-generation PDT.