Nitric Oxide Activatable Photodynamic Therapy Agents\nBased on BODIPY–Copper Complexes

In this work, two\nBODIPY–bipyridine Cu<sup>2+</sup> ion\ncomplexes for targeted nitric oxide (NO) activatable photodynamic\ntherapy are reported. The design is based on the relatively high concentration\nof these small gas molecules in the tumor microenvironment. Copper(II)\nion complexation to the photosensitizer renders it in the OFF position\nin terms of fluorescence and reactive oxygen species (ROS) production.\nThe interaction of the Cu<sup>2+</sup>–BODIPY complex with\nnitric oxide interchanges both fluorescence and therapy mode into\nthe ON state through the detachment of the cation. Therefore, targeting\nthe cancer cells would be expected to be achieved in this way. Moreover,\none of the compounds, <b>AP5</b>, has increased aqueous solubility\ndue to the polar structure. The designed structures also have near-infrared\n(IR) absorption ability up to 800 nm aqueous solutions. In addition,\nthrough using in vitro cell culture studies with HeLa and RAW264.7\ncell lines, we confirmed that <b>AP5</b> and <b>AP6</b> could be activated in the presence of NO, and cell photocytotoxicity\noccurred extensively compared with the NO-absent cells. We believe\nthat this work will provide new opportunities for the increased efficacy\nof the photodynamic treatment of cancer and smart photosensitizer\ndesign.