Direct Photocontrol of Peptidomimetics: An Alternative to Oxygen-Dependent Photodynamic Cancer Therapy

• Published in: Angewandte Chemie 2016-04, Vol.128 (18), p.5583-5586
• Main Authors: Babii, Oleg, Afonin, Sergii, Garmanchuk, Liudmyla V., Nikulina, Viktoria V., Nikolaienko, Tetiana V., Storozhuk, Olha V., Shelest, Dmytro V., Dasyukevich, Olga I., Ostapchenko, Liudmyla I., Iurchenko, Volodymyr, Zozulya, Sergey, Ulrich, Anne S., Komarov, Igor V.
• Format: Article
• Language: English
• Subjects: Animal models; Biocompatibility; Cancer; Cancer therapies; Cell death; Chemistry; Cytotoxicity; Derivatives; Gramicidin; Isomers; Krebs; Light; Oxygen; Peptidmimetika; Peptidomimetics; Photodynamische Therapie; Photoschalter; Reactive oxygen species; Solid tumors; Strategy; Therapy; Thermal stability; Toxicity; Tumor cells; Tumors; Wavelengths; Wirkstoffentwicklung
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.201600506

Conventional photodynamic treatment strategies are based on the principle of activating molecular oxygen in situ by light, mediated by a photosensitizer, which leads to the generation of reactive oxygen species and thereby causes cell death. A diarylethene‐derived peptidomimetic is presented that is suitable for photodynamic cancer therapy without any involvement of oxygen. This light‐sensitive molecule is not a mediator but is itself the cytotoxic agent. As a derivative of the cyclic amphiphilic peptide gramicidin S, the peptidomimetic exists in two thermally stable photoforms that are interconvertible by light of different wavelengths. The isomer generated by visible light shows much stronger toxicity against tumor cells than the UV‐generated isomer. First in vivo applications are demonstrated on a tumor animal model to illustrate how the peptidomimetic can be administered in the less toxic form and then activated locally in a solid tumor by visible light. Lichteffekte: Ein Peptidmimetikum mit Diarylethen‐Motiv eignet sich für eine sauerstoffunabhängige lichtgesteuerte Krebstherapie, weil das lichtresponsive Molekül nicht als Vermittler, sondern zytotoxisch wirkt. Das Gramicidin‐S‐Derivat liegt in zwei thermisch stabilen Formen vor: Das Isomer, das auf Bestrahlung mit sichtbarem Licht hin entsteht, ist deutlich stärker toxisch gegen Tumorzellen als das UV‐induzierte Isomer.