Better\nin the Near Infrared: Sulfonamide Perfluorinated-Phenyl\nPhotosensitizers for Improved Simultaneous Targeted Photodynamic Therapy\nand Real-Time Fluorescence Imaging

Tetraphenyloporphyrin\nderivatives are a useful scaffold for developing\nnew pharmaceuticals for photodynamic therapy (PDT) and the photodiagnosis\n(PD) of cancer. We synthesized new sulfonamide fluorinated porphyrin\nderivatives and investigated their potential as photosensitizers and\nreal-time bioimaging agents for cancer. We found that 5,10,15,20-tetrakis-[2′,3′,5′,6′-tetrafluoro-4′-methanesulfamidyl)phenyl]bacteriochlorin\n(<b>F</b><sub><b>4</b></sub><b>BMet</b>) has intense\nabsorption and fluorescence in the near-infrared, efficiently generates\nsinglet oxygen and hydroxyl radicals, has low toxicity in the dark,\nand high phototoxicity. We increased its bioavailability with encapsulation\nin Pluronic-based micelles, which also improved the photodynamic effect. <b>F</b><sub><b>4</b></sub><b>BMet</b> exhibits pH-dependent\nproperties (lower pH promoted its aggregation), and a GlyGly buffer\nwas used to effectively solubilize the compound. In vitro findings\nwith 2D cell culture were complemented with human-induced pluripotent\nstem cell (hiPSC)-derived organoids. <b>F</b><sub><b>4</b></sub><b>BMet</b> in <b>P123</b> micelles showed enhanced\nefficacy compared to <b>F</b><sub><b>4</b></sub><b>BMet</b> in the <b>GlyGly</b> formulation. <b>F</b><sub><b>4</b></sub><b>BMet</b> was further evaluated\nin real-time bioimaging and PDT of BALB/c mice bearing CT26 tumors.\nAfter <i>i.v.</i> injection, the photosensitizer was visible\nin the tumor area 3 h after injection. The most successful therapeutic\napproach proved to be tumor-targeted PDT using P123-encapsulated <b>F</b><sub><b>4</b></sub><b>BMet</b> illuminated 24\nh after administration with a light dose of 42 J/cm<sup>2</sup>, which\nled to a 30% long-term cure rate.