Carbon dot-assisted luminescence of singlet oxygen: the generation dynamics but not the cumulative amount of singlet oxygen is responsible for the photodynamic therapy efficacy

A novel carbon dot-based luminescence probe for singlet oxygen (O-1(2)) with a conventional optical detector has been implemented through the specific formation of electronically excited carbonyls from the breakdown of unstable endoperoxide intermediates, and its application in the real-time in vivo monitoring of O-1(2) in photodynamic therapy (PDT) is achieved. More attractively, the relationship between the dynamics details of photosensitizer-generated O-1(2) and the PDT efficacy has been established through a modified multiple-target survival model, enabling a direct and easy estimate of the surviving fraction of tumor cells from the generation dynamics of O-1(2). Both in vitro and in vivo therapy results revealed that the rapid generation dynamics of O-1(2) rather than its cumulative amount is responsible for better treatment efficacy in PDT. Overall, the deeper insight into the important roles of the generation dynamics of O-1(2) in the PDT efficacy is irreplaceably advantageous in substantially reduced risks from deleterious treatment-related side effects by screening advanced photosensitizers and determining the light exposure end point.