Renal-Clearable Porphyrinic Metal–Organic Framework Nanodots for Enhanced Photodynamic Therapy

Nanoscale porphyrinic metal-organic frameworks (NMOFs) have emerged as promising therapeutic platforms for the photodynamic therapy (PDT) of cancer in recent years. However, the relatively large sizes of current NMOFs ranging from tens to hundreds of nanometers usually lead to inefficient body clearance and unsatisfactory PDT effect, thus amplifying their long-term toxicity and restricting their further usage. To overcome these shortcomings, herein, ultrasmall porphyrinic metal-organic framework nanodots (MOF QDs) prepared from NMOFs are rationally synthesized via a facile method and used as renal-clearable nanoagents for the enhanced PDT of cancer. Compared with the precursor NMOFs, our well-prepared MOF QDs can generate 2-fold effective toxic reactive oxygen species (ROS) upon the same light irradiation and greatly decrease the inefficacy of PDT caused by the inefficient use of ROS generated from the interior of NMOFs. Meanwhile, the IC₅₀ value of ultrasmall MOF QDs is nearly one-third that of NMOFs, and in vivo results demonstrate that our MOF QDs exhibit better PDT efficacy than NMOFs under the same treatment owing to their overcoming the limited ROS diffusion distance. Significantly, these ultrasmall MOF QDs show efficient tumor accumulation and rapid renal clearance in vivo, indicating their potential in biomedical utility. Last but not least, comprehensive investigations of long-term toxicity of these MOF QDs well demonstrate their overall safety. Therefore, this study will offer valuable insight into the development of safe and high-performance PDT nanoplatforms for further clinical translation.