The biological activities of 5,15-diaryl-10,20-dihalogeno porphyrins for photodynamic therapy.

Autor: Li MY; Department of Pharmaceutical Science and Technology, College of Chemistry and Biology, Donghua University, Shanghai, 201620, China., Mi L; Department of Pharmaceutical Science and Technology, College of Chemistry and Biology, Donghua University, Shanghai, 201620, China., Meerovich G; Prokhorov General Physics Institute of the Russian Academy of Sciences, Moscow, 119435, Russia., Soe TW; Department of Pharmaceutical Science and Technology, College of Chemistry and Biology, Donghua University, Shanghai, 201620, China.; Department of Chemistry, University of Yangon, Yangon, 11041, Myanmar., Chen T; Department of Pharmaceutical Science and Technology, College of Chemistry and Biology, Donghua University, Shanghai, 201620, China., Than NN; Department of Chemistry, University of Yangon, Yangon, 11041, Myanmar., Yan YJ; Department of Pharmaceutical Science and Technology, College of Chemistry and Biology, Donghua University, Shanghai, 201620, China. y_yan11@sina.com., Chen ZL; Department of Pharmaceutical Science and Technology, College of Chemistry and Biology, Donghua University, Shanghai, 201620, China. zlchen1967@qq.com.; Department of Pharmacy, Huadong Hospital, Fudan University, Shanghai, 200040, China. zlchen1967@qq.com.
Jazyk: angličtina
Zdroj: Journal of cancer research and clinical oncology [J Cancer Res Clin Oncol] 2022 Sep; Vol. 148 (9), pp. 2335-2346. Date of Electronic Publication: 2022 May 06.
DOI: 10.1007/s00432-022-04037-7
Abstrakt: Purpose: Esophageal cancer is the most common gastrointestinal tumor and is difficult to be eradicated with conventional treatment. Porphyrin-based photosensitizers (PSs) mediated photodynamic therapy (PDT) could kill tumor cells with less damage to normal cells. As the most widely used porphyrin-based photosensitizer in clinics, Photofrin II has excellent anti-tumor effect. However, it has some disadvantages such as weak absorption at near infrared region, the complexity of components and prolonged skin photosensitivity. Here series novel 5,15-diaryl-10,20-dihalogeno porphyrin derivatives were afforded and evaluated to develop more effective and safer photosensitizers for tumor therapy.
Methods: The photophysical properties and singlet oxygen generation rates of 5,15-diaryl-10,20-dihalogeno porphyrins (I 1-6 , II 1-4 ) were tested. The cytotoxicity of I 1-6 and II 1-4 were measured by MTT assay. The pathway of cell death was studied by flow cytometry. In vivo photodynamic efficacy of I 3 and II 2-4 in Eca-109 tumor-bearing BABL/c nude mice were measured and histopathological analysis were examined.
Results: 5,15-Diaryl-10,20-dihalogeno porphyrins I 1-6 and II 1-4 were synthesized. The longest absorption wavelength of these halogenated porphyrins (λ max  = 660 nm) displayed a red shift around 30 nm compared to the unhalogenated porphyrins PS 1 (λ max  = 630 nm). The singlet oxygen generation rates of I 1-6 and II 1-4 were significantly higher than PS 1 and HMME. All PSs mediated PDT showed obvious cytotoxic effect against Eca-109 cells compared to HMME in vitro and in vivo. Among these PSs, II 4 exhibited appropriate absorption in the phototherapeutic window, higher 1 O 2 generation rate (k = 0.0061 s -1 ), the strongest phototoxicity (IC 50  = 0.4 μM), lower dark toxicity, high generation of intracellular ROS in Eca-109 cells and excellent photodynamic anti-tumor efficacy in vivo. Besides, cell necrosis was induced by compound II 4 mediated PDT.
Conclusion: All new compounds have obvious photodynamic anti-esophageal cancer effects. Among them, the photosensitizer II 4 showed excellent efficacy in vitro and in vivo, which has the potential to become a photodynamic anti-tumor drug.
(© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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