Amplifying Free Radical Generation of AIE Photosensitizer with Small Singlet-Triplet Splitting for Hypoxia-Overcoming Photodynamic Therapy

作者：Xiao, Ya-Fang; Chen, Wen-Cheng; Chen, Jia-Xiong; Lu, Guihong^*; Tian, Shuang; Cui, Xiao; Zhang, Zhen; Chen, Huan; Wan, Yingpeng; Li, Shengliang^*; Lee, Chun-Sing^*

来源：ACS applied materials & interfaces, 2022, 14(4): 5112-5121.

DOI：10.1021/acsami.1c23797

• type-I photodynamic therapy
• aggregate-induced emission
• hypoxia
• singlet-triplet splitting
• electron-rich group

Type-I photodynamic therapy (PDT) with less oxygen consumption shows great potential for overcoming the vicious hypoxia typically observed in solid tumors. However, the development of type-I PDT is hindered by insufficient radical generation and the ambiguous design strategy of type-I photosensitizers (PSs). Therefore, developing highly efficient type-I PSs and unveiling their structure-function relationship are still urgent and challenging. Herein, we develop two phenanthro[9,10-d]imidazole derivatives (AQPO and AQPI) with aggregation-induced emission (AIE) characteristics and boost their reactive oxygen species (ROS) generation efficiency by reducing singlet-triplet splitting (Delta E-ST). Both AQPO and AQPI show ultrasmall Delta E-ST values of 0.09 and 0.12 eV, respectively. By incorporating electron-rich anisole, the categories of generated ROS by AIE PSs are changed from type-II (singlet oxygen, O-1(2)) to type-I (superoxide anion radical, O-2(center dot-) and hydroxyl radical, center dot OH). We demonstrate that the assembled AQPO nanoparticles (NPs) achieve a 3.2- and 2.9-fold increase in the O-2(center dot-) and center dot OH generation efficiencies, respectively, compared to those of AQPI NPs (without anisole) in water, whereas the O-1(2) generation efficiency of AQPO NPs is lower (0.4-fold) than that of AQPI NPs. The small Delta E-ST and anisole group endow AQPO with an excellent capacity for type-I ROS generation. In vitro and in vivo experiments show that AQPO NPs achieve an excellent hypoxia-overcoming PDT effect by efficiently eliminating tumor cells upon white light irradiation with good biosafety.

• 单位
  中国科学院; 苏州大学; 广东工业大学