Controlled Generation of Singlet Oxygen in Living Cells with Tunable Ratios of the Photochromic Switch in Metal-Organic Frameworks

Development of a photosensitizing system that can reversibly control the generation of singlet oxygen (O-1(2)) is of great interest for photodynamic therapy (PDT). Recently several photosensitizer-photochromic-switch dyads were reported as a potential means of the O-1(2) control in PDT. However, the delivery of such a homogeneous molecular dyad as designed (e.g., optimal molar ratio) is extremely challenging in living systems. Herein we show a Zr-MOF nanoplatform, demonstrating energy transfer-based O-1(2) controlled PDT. Our strategy allows for tuning the ratios between photosensitizer and the switch molecule, enabling maximum control of O-1(2) generation. Meanwhile, the MOF provides proximal placement of the functional entities for efficient intermolecular energy transfer. As a result, the MOF nanoparticle formulation showed enhanced PDT efficacy with superior O-1(2) control compared to that of homogeneous molecular analogues.