Mitochondria‐Targeted Nanoscale MOFs for Improved Photodynamic Therapy

Abstract

Due to the existence of hypoxic microenvironment, the efficacy of photodynamic therapy (PDT) is frequently weakened. As a result, targeted treatment toward oxygenrich 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 ZrÀ OÀ P bonding, a dense coverage of phosphonate-conjugating targeting molecules on NMOFs is obtained and each surficial unsaturated ZrÀ 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 dualtargeting NMOFs is significantly improved with a low IC 50 of 0.74 μM 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.

Expanding the Limits of Photodynamic Therapy: The Design of Organelles and Hypoxia-Targeting Nanomaterials for Enhanced Photokilling of Cancer

“…Thus, phosphorylation of TPP is an efficient strategy for immobilization onto MOFs. On the basis of this concept, Gong et al presented a universal and simple surface modification method for nano MOFs . The phosphorylation of bioactive compounds was simply obtained by incubating DCC-activated bioactive compounds (TPP and FA) with alendronate for 12 h in DMF/DMSO under stirring in the absence of light.…”

“…On the basis of this concept, Gong et al presented a universal and simple surface modification method for nano MOFs. 202 The phosphorylation of bioactive compounds was simply obtained by incubating DCC-activated bioactive compounds (TPP and FA) with alendronate for 12 h in DMF/DMSO under stirring in the absence of light. Conjugations of phosphorylated bioactive molecules were achieved by mixing Zr-MOFs in DMF for eight hours under dark conditions.…”

Biomedical Applications of Metal–Organic Frameworks at the Subcellular Level

“…Reproduced with permission. [ 74 ] Copyright 2019, Wiley‐VCH. d) Illustration of the Au‐Cy3P@ZIF‐8 nanoprobe turn‐on strategy in lysosome.…”

“…The proposed phosphorylation modification strategy paves the way for the immobilization of other functional groups on NMOFs for targeting of various organelles and improvement of therapy efficacy. [ 74 ]…”

Highly selective fluorescent turn-on–off sensing of OH−, Al3+ and Fe3+ ions by tuning ESIPT in metal organic frameworks and mitochondria targeted bio-imaging

“…37 MOF based selective labelling of organelles such as mitochondria 38 is one of the current trending topics due to its signicant contribution in understanding the proper functioning of the organelles in cellular system. 39,40 Several MOFs with ESIPT based uorescent characteristics have been previously reported. 41 Although MOF based ESIPT tuned sensing mechanisms of metal ions 42 were rarely explored.…”