Nature Communications articleRationally designed ruthenium complexes for 1- and 2-photon photodynamic therapy Open Access
Published: 26 June 2020
Johannes Karges, Shi Kuang, Federica Maschietto, Olivier Blacque, Ilaria Ciofini, Hui Chao & Gilles Gasser
Abstract
The use of photodynamic therapy (PDT) against cancer has received increasing attention over recent years. However, the application of the currently approved photosensitizers (PSs) is limited by their poor aqueous solubility, aggregation, photobleaching and slow clearance from the body. To overcome these limitations, there is a need for the development of new classes of PSs with ruthenium(II) polypyridine complexes currently gaining momentum. However, these compounds generally lack significant absorption in the biological spectral window, limiting their application to treat deep-seated or large tumors. To overcome this drawback, ruthenium(II) polypyridine complexes designed in silico with (E,E′)-4,4′-bisstyryl-2,2′-bipyridine ligands show impressive 1- and 2-Photon absorption up to a magnitude higher than the ones published so far. While nontoxic in the dark, these compounds are phototoxic in various 2D monolayer cells, 3D multicellular tumor spheroids and are able to eradicate a multiresistant tumor inside a mouse model upon clinically relevant 1-Photon and 2-Photon excitation.
Introduction
Due to the increasing impact of cancer on the life quality and mortality of humans, increasing research efforts are devoted toward the development of anticancer drugs and strategies. Among the most commonly used techniques to fight this disease (i.e., surgery, chemotherapy, and radiotherapy), photodynamic therapy (PDT) is receiving increasing attention during the last decades. In PDT, a photosensitizer (PS) is activated upon light irradiation to generate reactive oxygen species (ROS). As the majority of currently approved PSs are based on tetrapyrrolic structures (i.e., porphyrin, chlorin, and phthalocyanine), these compounds share similar drawbacks (e.g., poor aqueous solubility, aggregation, photobleaching, slow clearance from the body, and hepatotoxicity). To overcome these limitations, there is a need for the development of new classes of PSs. Among others, the use of transition metal complexes and especially, Ru(II) polypyridine complexes are gaining momentum due to their attractive photophysical and chemical properties (i.e., strong luminescence, high singlet oxygen production, high chemical, and photophysical stability) with the compound TLD-1433 having just entered phase II clinical trials for the treatment of non-muscle invasive bladder cancer..........................................