Nanoscale Mixed-Component Metal–Organic Frameworks with Photosensitizer Spatial-Arrangement-Dependent Photochemistry for Multimodal-Imaging-Guided Photothermal Therapy

The introduction of multiple components into one crystalline metal–organic framework (MOF) provides a feasible approach to fully understand the correlation of component heterogeneity and the whole performance. Herein, photoactive tetratopic chlorin (TCPC) ligands with different geometry and connectivity have been successfully incorporated into the Hf-UiO-66 archetype structure without altering the underlying topology by a facile strategy. Unlike previous porphyrin-nanoscale-MOFs (porphyrin-NMOFs) with homogeneous periodical porphyrin arrangements typically for photodynamic therapy (PDT) usage, we demonstrate that TCPC component heterogeneity within as-synthesized TCPC-UiO possesses both PDT and photothermal therapy (PTT) simultaneously, but PTT takes a more potent antitumor efficacy as proven in several photophysical characterizations and biological experiments in vitro. The high photothermal conversion efficiency, favorable photostability and biocompatibility, and strong X-ray attenuating ability of the Hf element within TCPC-UiO make it a potential platform for further application in multimodal CT/thermal/photoacoustic imaging. Additionally, TCPC-UiO shows an impressive anticancer activity against H22 tumor-bearing mice in vivo, and its tumor inhibition rate is above 90%. We anticipate that the current work may offer in-depth insight into the component heterogeneity and property relationship and also extend biological applications of NMOFs.