Photodynamic** (PDT) is an emerging non-invasive approach to cancer** that relies heavily on the presence of highly efficient photosensitizers (PS) and adequate oxygen**. However, in the hypoxic microenvironment, the poor solubility, aggregation tendency and hypoxia of solid tumors during the photodynamic period seriously affected the ** effect of PS.
Recently,Department of Chemical Engineering and Biotechnology, University of Cambridged**idfairen-jimenezTeam of professorsA metallic zirconium organic framework based on fluorinated bodipy was constructed for in vivo enhanced photodynamics**. The study, titled "Afluorinated Bodipy-Based Zirconium Metal-Organic Framework for Invivo Enhanced Photodynamic Therapy," was published in the Journal of the American Chemical Society.
In the present study, the authors first synthesized a Bodipy-based ZR-MOF, i.e., 69-L2, by post-synthetic ligand exchange (PSE). Due to the appropriate ligand length, the authors chose 2-fold interpenetrating 69-Me2 as the parent MOF for PSE. The PSE process occurs in a single-crystal-to-single-crystal (SC-SC) fashion, and importantly, single-crystal X-ray diffraction (SCXRD) confirms the successful binding of the two-position Bodipy-derived ligand. To alleviate hypoxia in future PDT in vivo experiments, the authors introduced a perfluorooctyl group into a hydrophilic phosphate-functionalized methoxy polyethylene glycol and attached it to the outer surface of 69-L2 to form 69-l2@f. Under LED irradiation, the new system not only exhibited excellent oxygen carrying capacity, but also increased ROS generation capacity compared to control 69-l2@p lacking fluorine functionalization. The authors then combined confocal laser scanning microscopy (CLSM) imaging and transmission electron microscopy (TEM) to examine the internalization of 69-L2, 69l2@p, and 69-l2@f in triple-negative breast cancer MDAMB-231 cells. In in vitro studies under normoxic and hypoxic conditions, the authors demonstrated enhanced PDT effect at 69-l2@fvs69-l2@p. Finally, in vivo studies in a triple-negative, luciferase-expressing MDA-MB-231 breast cancer mouse model showed that the 69-l2@f system combined with hydrogel had a significant photodynamic effect on locally active tumor growth inhibition under LED illumination.
Schematic diagram 1Bodipy-based ZR-MOF provides hypoxic relief and maximizes efficacy during PDT in vivo.
Figure 1Synthesis and structure diagram of 69-L2.
Figure 2Characterization of 69-L2, 69-l2@p and 69-l2@f
Figure 3Biocompatibility and intracellular uptake of 69-L-l2@p and 69-l2@f.
Figure 4ROS generation of 69-l2@p and 69-l2@f.
Figure 5Schematic diagram of the in vivo study.
Figure 6Live imaging of a Hydrogel or 69-l2@fgel pair of Triple Negative Breast Tumor xenografted BalbC female nude mice under green LED irradiation.
Taken together, this work not only constructs a gentle method for the preparation of Bodipy-based ZR-MOFs and further alleviates tumor hypoxia by in-situ oxygenation, but also highlights an in vivo delivery strategy that combines the photodynamic effects of 69-l2@f with hydrogels, resulting in a substantial reduction in tumor growth, making it possible to use this as a more effective alternative to conventional cancer.
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