Fluorescence Lifetime Imaging-Guided Photodynamic Therapy over Two-Photon Responsive Metal-Organic Frameworks

In the realm of photodynamic therapy (PDT), the incorporation of real-time feedback through two-photon fluorescence lifetime imaging poses a significant challenge, primarily due to the intricate nature of photosensitizer design. In our investigation, we have effectively constructed a versatile platform labeled as ZTBH using a post-ligand modification approach, resulting in enhanced two-photon fluorescence capabilities and notable responsiveness of fluorescence lifetime to variations in the cellular microenvironment. The distinctive synergy between intersystem crossing and linker-to-cluster charge transfer within ZTBH empowers the generation of ample reactive oxygen species (1O2 and O2•-), thereby yielding remarkable efficiency in PDT. Moreover, the capping of hyaluronic acid (HA) through coordination method confers ZTBH with cancer-specific targeting properties. Subsequently, with the aid of a two-photon fluorescence lifetime imaging microscope (TP-FLIM), ZTBH not only achieves successful two-photon photodynamic therapy but also enables real-time visualization of cellular microenvironment changes throughout the apoptosis process. This investigation underscores a viable approach in the creation of two-photon fluorescence lifetime photosensitizers for visualizing the PDT procedure.