Heavy-atom-free π-twisted photosensitizers for fluorescence bioimaging and photodynamic therapy

As the field of preclinical research on photosensitizers (PSs) for anticancer photodynamic therapy (PDT) continues to expand, a focused effort is underway to develop agents with innovative molecular structures that offer enhanced targeting, selectivity, activation, and imaging capabilities. In this context, we introduce two new heavy-atom-free PSs, DBXI and DBAI, characterized by a twisted π-conjugation framework. This innovative approach enhances the spin–orbit coupling (SOC) between the singlet excited state (S1) and the triplet state (T1), resulting in improved and efficient intersystem crossing (ISC). Both PSs are highly effective in producing reactive oxygen species (ROS), including singlet oxygen and/or superoxide species. Additionally, they also demonstrate remarkably strong fluorescence emission. Indeed, in addition to providing exceptional photocytotoxicity, this emissive feature, generally lacking in other reported structures, allows for the precise monitoring of the PSs’ distribution within specific cellular organelles even at nanomolar concentrations. These findings underscore the dual functionality of these PSs, serving as both fluorescent imaging probes and light-activated therapeutic agents, emphasizing their potential as versatile and multifunctional tools in the field of PDT.随着抗癌光动力治疗（photodynamic therapy, PDT）用光敏剂（photosensitizers, PSs）的临床前研究领域持续拓展，开发具有创新分子结构、可实现更强靶向性、选择性、激活能力与成像性能的制剂的工作正有序推进。在此背景下，我们报道两种新型无重原子光敏剂DBXI与DBAI，二者均具有扭曲π共轭骨架。这一创新设计可增强单重激发态（S1）与三重激发态（T1）之间的自旋轨道耦合（spin–orbit coupling, SOC），进而实现高效的系间窜越（intersystem crossing, ISC）。两种光敏剂均能高效产生活性氧（reactive oxygen species, ROS），包括单线态氧和/或超氧物种。此外，它们还展现出极强的荧光发射特性。值得注意的是，除了具备优异的光细胞毒性外，这类其他已报道结构普遍缺失的发光特性，使得即便在纳摩尔浓度下，也可精准监测光敏剂在特定细胞细胞器内的分布情况。上述研究结果凸显了这两种光敏剂的双重功能：既可作为荧光成像探针，又可作为光激活治疗剂，彰显了其作为多功能工具在光动力治疗领域的应用潜力。