期刊
CHEMISTRY-A EUROPEAN JOURNAL
卷 27, 期 1, 页码 362-370出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/chem.202003486
关键词
bioinorganic chemistry; medicinal inorganic chemistry; metals in medicine; photodynamic therapy; photosensitizers
资金
- ERC [GA 681679]
- ANR [ANR-10-IDEX-0001-02]
- National Science Foundation of China [21525105, 21778079]
- 973 Program [2015CB856301]
In recent years, photodynamic therapy (PDT) has gained attention as a treatment for certain types of cancer. This study tested a series of new Ru-II polypyridine complexes as photosensitizers on large 3D multicellular tumor spheroids (MCTSs) to mimic conditions found in clinical tumors. The lead compound showed impressive phototoxicity in eradicating the hypoxic center of the tumors, demonstrating efficacy not only in vitro but also in mice models with adenocarcinomic human alveolar basal epithelial tumors.
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 tumor center. To mimic the conditions found in clinical tumors, exceptionally large 3D multicellular tumor spheroids (MCTSs) with a diameter of 800 mu m were used in this work to test a series of new Ru-II polypyridine complexes as one-photon and two-photon PSs. These metal complexes were found to fully penetrate the 3D cellular architecture and to generate singlet oxygen in the hypoxic center upon light irradiation. While having no observed dark toxicity, the lead compound of this study showed an impressive phototoxicity upon clinically relevant one-photon (595 nm) or two-photon (800 nm) excitation with a full eradication of the hypoxic center of the MCTSs. Importantly, this efficacy was also demonstrated on mice bearing an adenocarcinomic human alveolar basal epithelial tumor.
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