UNAM-National Nanotechnology Research Center, Bilkent University, 06800, Ankara, Turkey.
Department of Chemistry, Bilkent University, 06800, Ankara, Turkey.
Angew Chem Int Ed Engl. 2016 Feb 18;55(8):2875-8. doi: 10.1002/anie.201511345. Epub 2016 Jan 22.
The photosensitized generation of singlet oxygen within tumor tissues during photodynamic therapy (PDT) is self-limiting, as the already low oxygen concentrations within tumors is further diminished during the process. In certain applications, to minimize photoinduced hypoxia the light is introduced intermittently (fractional PDT) to allow time for the replenishment of cellular oxygen. This condition extends the time required for effective therapy. Herein, we demonstrated that a photosensitizer with an additional 2-pyridone module for trapping singlet oxygen would be useful in fractional PDT. Thus, in the light cycle, the endoperoxide of 2-pyridone is generated along with singlet oxygen. In the dark cycle, the endoperoxide undergoes thermal cycloreversion to produce singlet oxygen, regenerating the 2-pyridone module. As a result, the photodynamic process can continue in the dark as well as in the light cycles. Cell-culture studies validated this working principle in vitro.
光动力疗法（PDT）过程中，肿瘤组织内的单线态氧的光敏生成是自我限制的，因为在该过程中，肿瘤内已经较低的氧气浓度进一步降低。在某些应用中，为了最大限度地减少光诱导缺氧，光被间歇性地引入（分数 PDT），以允许细胞氧气补充的时间。这种情况延长了有效治疗所需的时间。在此，我们证明了具有用于捕获单线态氧的附加 2-吡啶酮模块的光敏剂在分数 PDT 中是有用的。因此，在光循环中，2-吡啶酮的内过氧化物与单线态氧一起生成。在暗循环中，内过氧化物经历热环回转化产生单线态氧，使 2-吡啶酮模块再生。因此，光动力过程可以在黑暗中和光循环中继续进行。细胞培养研究在体外验证了这一工作原理。
