Mallinckrodt Institute of Radiology, Washington University School of Medicine, 4515 McKinley Avenue, Saint Louis, MO, 63130, USA.
Biomedical Engineering, Washington University in Saint Louis, 1 Brookings Drive, Saint Louis, MO, 63130, USA.
Angew Chem Int Ed Engl. 2017 Aug 28;56(36):10717-10720. doi: 10.1002/anie.201704458. Epub 2017 Jul 26.
Photodynamic therapy (PDT) is widely used to treat diverse diseases, but its dependence on oxygen to produce cytotoxic reactive oxygen species (ROS) diminishes the therapeutic effect in a hypoxic environment, such as solid tumors. Herein, we developed a ROS-producing hybrid nanoparticle-based photosensitizer capable of maintaining high levels of ROS under both normoxic and hypoxic conditions. Conjugation of a ruthenium complex (N3) to a TiO nanoparticle afforded TiO -N3. Upon exposure of TiO -N3 to light, the N3 injected electrons into TiO to produce three- and four-fold more hydroxyl radicals and hydrogen peroxide, respectively, than TiO at 160 mmHg. TiO -N3 maintained three-fold higher hydroxyl radicals than TiO under hypoxic conditions via N3-facilitated electron-hole reduction of adsorbed water molecules. The incorporation of N3 transformed TiO from a dual type I and II PDT agent to a predominantly type I photosensitizer, irrespective of the oxygen content.
光动力疗法（PDT）被广泛用于治疗多种疾病，但它对氧气的依赖性使其在缺氧环境（如实体瘤）中产生细胞毒性活性氧（ROS）的效果减弱。在此，我们开发了一种能够在常氧和缺氧条件下都保持高水平 ROS 的基于产 ROS 杂化纳米颗粒的光敏剂。将钌配合物（N3）与 TiO 纳米颗粒连接，得到 TiO-N3。TiO-N3 暴露于光线下时，N3 将电子注入 TiO 中，分别产生比 TiO 多三倍和四倍的羟基自由基和过氧化氢，在 160 mmHg 时。通过 N3 促进吸附水分子的电子-空穴还原，TiO-N3 在缺氧条件下保持比 TiO 高三倍的羟基自由基。N3 的掺入将 TiO 从双Ⅰ型和Ⅱ型 PDT 剂转变为主要的Ⅰ型光敏剂，与氧气含量无关。
