Key Lab of Organic Optoelectronics and Molecular Engineering, Department of Chemistry, Tsinghua University, Beijing 100084, People's Republic of China.
ACS Appl Mater Interfaces. 2020 Jun 17;12(24):26982-26990. doi: 10.1021/acsami.0c07471. Epub 2020 Jun 3.
Photodynamic therapy (PDT) is a promising approach for the treatment of different kinds of cancers as well as some other diseases. By combining spatiotemporal light irradiation with photosensitizers (PS), PDT can be easily controlled by tuning illumination time and sites of irradiation. However, how to reduce the phototoxicity of the PS to normal cells without sacrificing its effectiveness to cancer cells is still a challenge. Herein, we put forward a deactivation and reactivation strategy for PDT to reduce the undesired damage to normal cells under light irradiation. First, by chemical modification of -(4-pyridinyl)-substitution BODIPY with phenylboronic acid pinacol ester moiety, the masked PS ProBODIPY-2I with low generation efficiency of singlet oxygen and good water solubility can be obtained. Moreover, ProBODIPY-2I can be reactivated at tumor microenvironment by reactive oxygen species (ROS), resuming their PDT efficiency. Meanwhile, ProBODIPY-2I showed low phototoxicity for the normal cells, due to the relatively low concentration of ROS. In this way, the safety and selectivity for the PDT can be greatly improved. It is anticipated that some other tumor biomarkers, such as proton, GSH and enzymes, can be employed for the smart PDT methods.
光动力疗法（PDT）是一种有前途的治疗方法，可以治疗不同类型的癌症以及其他一些疾病。通过将时空光照射与光敏剂（PS）结合，PDT 可以通过调整照射时间和照射部位来轻松控制。然而，如何在不牺牲对癌细胞的有效性的情况下降低 PS 对正常细胞的光毒性仍然是一个挑战。在此，我们提出了一种 PDT 的失活和再激活策略，以减少光照射下正常细胞的不必要损伤。首先，通过对 -(4-吡啶基)-取代 BODIPY 进行苯硼酸频哪醇酯部分的化学修饰，可以得到具有低单线态氧生成效率和良好水溶性的掩蔽 PS ProBODIPY-2I。此外，ProBODIPY-2I 可以在肿瘤微环境中被活性氧（ROS）重新激活，恢复其 PDT 效率。同时，由于 ROS 的浓度相对较低，ProBODIPY-2I 对正常细胞的光毒性较低。通过这种方式，可以大大提高 PDT 的安全性和选择性。预计其他一些肿瘤生物标志物，如质子、GSH 和酶，可以用于智能 PDT 方法。
