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1- and 2-Photon Phototherapeutic Effects of Ru(II) Polypyridine Complexes in the Hypoxic Centre of Large Multicellular Tumour Spheroids and Tumour-Bearing Mice

preprint
submitted on 05.06.2020 and posted on 08.06.2020 by Johannes Karges, Shi Kuang, Yih Ching Ong, Hui Chao, Gilles Gasser
During the last decades, photodynamic therapy (PDT), an approved medical technique, has received increasing attention to treat certain types of cancer. Despite recent improvements, the treatment of large tumors remains a major clinical challenge due to the low ability of the photosensitizer (PS) to penetrate a 3D cellular architecture and the low oxygen concentrations present in the tumour centre. To mimic the conditions found in clinical tumors, exceptionally large 3D multicellular tumour spheroids (MCTSs) with a diameter of 800 µm were used in this work to test a series of new Ru(II) polypyridine complexes as 1-Photon and 2-Photon PSs. These metal complexes were found to fully penetrate the 3D cellular architecture and to generate singlet oxygen in the hypoxic centre upon light irradiation. While having no observed dark toxicity, the lead compound of this study showed an impressive phototoxicity upon clinically relevant 1-Photon (595 nm) or 2-Photon (800 nm) excitation with a full eradication of the hypoxic centre of the MCTSs. Importantly, this efficacy was also demonstrated on mice bearing an adenocarcinomic human alveolar basal epithelial tumour.

Funding

European Research Council

Agence Nationale de la Recherche

National Science Foundation of China

973 Program

History

Email Address of Submitting Author

gilles.gasser@chimieparistech.psl.eu

Institution

Chimie ParisTech, PSL University, CNRS, Institute of Chemistry for Life and Health Sciences

Country

France

ORCID For Submitting Author

0000-0002-4244-5097

Declaration of Conflict of Interest

None

Exports