The severe hypoxia in solid tumor and the accurate discrimination between cancer and normal cells gravely restrict the application of fluorescence imaging-guided photodynamic therapy (PDT), although this cancer-therapy modality has significant superiorities in terms of precise visualization of the location of photosensitizers (PSs) in tumor tissue as well as noninvasive and reliable treatment. A convenient and universal fluorescence system featuring Type I reactive oxygen species (ROS) based on free radicals, wide-spectrum cancer cell discrimination and distinctive aggregation-induced emission (AIE) characteristics could offer a feasible approach to resolve the problems above, which is yet extremely challenging. Herein, we propose a series of electron-rich anion-π⁺ AIE-active luminogens (AIEgens) fabricating increasingly stronger intermolecular charge transfer (ICT) state to promote highly efficient intersystem crossing for boosting Type I ROS generation. Moreover, MeOTPPM has priority to enter cancer cells with better plasma membrane permeability due to the strongest binding force with water molecules. This work serves as a pioneering reference for rationally constructing Type I-based purely organic PSs to overcome tumor hypoxia defects in PDT and selectively targeting and ablating cancer cells over normal cells without the aid of any extra cancer cell-specific targeting ligands.

实体瘤中的严重缺氧以及癌症与正常细胞之间的精确区分严重限制了荧光成像引导光动力疗法（PDT）的应用，尽管这种癌症疗法在精确显示光敏剂位置方面具有显着优势（ PSs）以及无创且可靠的治疗方法。一种方便且通用的荧光系统，具有基于自由基的I型活性氧（ROS），广谱癌细胞辨别力和独特的聚集诱导发射（AIE）特性，可以为解决上述问题提供可行的方法，目前尚无极具挑战性。在这里，我们提出了一系列富电子阴离子-π ⁺AIE活性发光剂（AIEgens）逐渐形成更强的分子间电荷转移（ICT）状态，以促进高效的系统间交叉，从而促进I型ROS的产生。此外，由于与水分子的最强结合力，MeOTPPM优先进入具有更好质膜渗透性的癌细胞。这项工作为合理构建基于I型的纯有机PS，以克服PDT中的肿瘤缺氧缺陷并在不借助任何癌细胞特异性靶向配体的情况下选择性靶向和消融正常细胞上的癌细胞提供了开创性参考。