Mitochondria-Targeted Nanoscale MOFs for Improved Photodynamic Therapy

Due to the existence of hypoxic microenvironment, the efficacy of photodynamic therapy (PDT) is frequently weakened. As a result, targeted treatment toward oxygen-rich mitochondria is considered as a promising cancer therapy. Herein, both triphenylphosphine (TPP) and folic acid (FA) are simultaneously grafted onto nanoscale metal-organic frameworks (NMOFs) to realize dual-targeting delivery of the nanoplatforms into cancer cells and their mitochondria via the proposed phosphorylation modification strategy. A large amount of highly efficient photosensitizer of porphyrinic molecules is integrated into the NMOFs with a uniform particle size of about 65 nm. Thanks to the strong Zr-O-P bonding, a dense coverage of phosphonate-conjugating targeting molecules on NMOFs is obtained and each surficial unsaturated Zr-O cluster is adequately occupied. The resultant dual-targeting NMOFs feature high biostability and biocompatibility, as well as improved cellular uptake and mitochondrial accumulation. The PDT efficacy of these dual-targeting NMOFs is significantly improved with a low IC50 of 0.74 mu M upon 10 min light radiation, which is at least four times higher than that of non-targeting counterparts. This phosphorylation strategy would be hopeful for immobilizing a variety of biogenic groups on NMOFs to make them targetable to various specific organelles and to improve the therapy efficacy on related diseases.