Studying the Cellular Distribution of Highly Phototoxic Platinated Metalloporphyrins Using Isotope Labelling

Abstract

We report the synthesis of novel tetraplatinated metalloporphyrin-based photosensitizers (PSs) for photodynamic therapy (PDT), their characterization, cellular uptake and localization, as well as the determination of their <i>in vitro</i> light-induced anticancer properties. The PSs show excellent phototoxic indexes up to 5800 against HeLa cells, which is, to the best of our knowledge, the highest value reported for any porphyrin so far. Furthermore, isotopic labelling of the porphyrin with a highly enriched <sup>67</sup>Zn isotope was performed in order to determine the distribution ratio of zinc to platinum by ICP-MS, allowing to differentiate between naturally occurring zinc and <sup>67</sup>Zn that was introduced into the cells by the PS. We conclude that the platinum units within the platinum-PS conjugates help to solubilize the PS and, at the same time, act as cell-penetrating vectors, enhancing the efficiency of the PS without causing a significant dark toxicity.<br>

BODIPY-Based Photothermal Agents with Unprecedented Phototoxic Indices for Cancer Treatment

“…S3) based on a direct method (S9). 36,[39][40][41][42] Fluorescence quantum yields ( F ) (Tab. 36,[43][44][45] This correlates with the triplet state lifetimes ( T ) (Tab.…”

Unraveling the Photodynamic Activity of Cationic Benzoporphyrin-Based Photosensitizers against Bladder Cancer Cells

“…Concerning the modification of porphyrins and related compounds with platinum(II), most of the modifications reported in the literature describe the metalation of the tetrapyrrolic core with Pt(II) leading to the corresponding metalloporphyrinoid [ 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 ]. A literature survey also shows a considerable number of papers describing the preparation of porphyrin-platinum complexes by modification of peripheral moieties at meso positions, mainly by attachment of cyclometalated platinum units to pyridyl moieties [ 20 , 59 , 67 , 68 , 69 , 70 , 71 , 72 , 73 ]. Analogue synthetic approaches were also reported to modify corroles [ 74 , 75 ] and phthalocyanines [ 76 , 77 , 78 , 79 , 80 ].…”