Engineered photosynthetic prokaryotes for cancer therapy: From natural functions to programmable therapeutic platforms

Photosynthetic prokaryotes (PPs) combine tumor tropism with light-driven energy conversion and metabolic regulation, offering a unique living platform for cancer therapy. PPs include oxygenic cyanobacteria and anoxygenic photosynthetic bacteria (PSB), which differ in photosystems, oxygen metabolism, and light utilization, leading to distinct therapeutic functions and applications. Rather than serving only as delivery vehicles, PPs act as metabolically active therapeutic agents that exert antitumor effects through photodynamic and photothermal effects, hydrogen production, TME remodeling, and immune activation, thereby enhancing multiple anticancer modalities. This review summarizes the biological basis and intrinsic antitumor mechanisms of PPs, highlights the differences between cyanobacteria and PSB, and discusses engineering strategies for targeting and navigation, payload and delivery, and in situ drug production. It further reviews their applications in chemotherapy, radiotherapy, immunotherapy, phototherapy, and sonodynamic therapy, compares administration routes, and discusses translational challenges.