Repurposing methylene blue as activatable prodrugs for precise disease theranostics

This review systematically summarizes recent advances in activatable prodrugs based on methylene blue (MB) for disease theranostics. Owing to its long-standing clinical use, well-characterized safety profile, and intrinsic optical properties, MB has emerged as an ideal molecular scaffold for constructing theranostic prodrugs that integrate near-infrared fluorescence/photoacoustic (NIRF/PA) imaging with photodynamic/sonodynamic therapy (PDT/SDT). By responding to specific enzymes, redox conditions, or exogenous physical stimuli, MB-based prodrugs achieve "off-on" activation, enabling precise therapeutic release while simultaneously generating diagnostic signals. This review highlights representative applications in oncology, inflammatory diseases, and infectious diseases, elucidates the underlying activation mechanisms and synergistic therapeutic potential, and provides design principles for the development of multimodal theranostic strategies.