Hao Boyi, Wang Jiaxin, Wang Chao, Xue Ke, Xiao Minghui, Lv Shuyi, Zhu Chunlei
Key Laboratory of Functional Polymer Materials of Ministry of Education, State Key Laboratory of Medicinal Chemical Biology, Institute of Polymer Chemistry, College of Chemistry, Nankai University Tianjin 300071 China
Chem Sci. 2022 Mar 14;13(14):4139-4149. doi: 10.1039/d2sc00381c. eCollection 2022 Apr 6.
Photodynamic therapy (PDT) has attracted much attention in disease treatments. However, the exploration of a novel method for the construction of outstanding photosensitizers (PSs) with stimuli-responsiveness remains challenging. In this study, we, for the first time, report a novel and effective strategy to boost reactive oxygen species (ROS) generation by bridging donor-acceptor (D-A) type PSs with the azo group. In contrast to the counterpart without azo-bridging, the azo-bridged PSs exhibit remarkably enhanced ROS generation both type-I and type-II photochemical reactions. Theoretical calculations suggest that azo-bridging leads to a prominent reduction in Δ , thereby enabling enhanced ROS generation efficient intersystem crossing (ISC). The resulting azo-bridged PS (denoted as Azo-TPA-Th(+)) exhibits a particularly strong bactericidal effect against clinically relevant drug-resistant bacteria, with the killing efficiency up to 99.999999% upon white light irradiation. Since azo-bridging generates an azobenzene structure, Azo-TPA-Th(+) can undergo -to- isomerization upon UV irradiation to form emissive aggregates by shutting down the ISC channel. By virtue of the fluorescence turn-on property of unbound Azo-TPA-Th(+), we propose a straightforward method to directly discern the effective photodynamic bactericidal dose without performing the tedious plate-counting assay. This study opens a brand-new avenue for the design of advanced PSs with both strong ROS generation and stimuli-responsiveness, holding great potential in high-quality PDT with rapid prediction of the therapeutic outcome.
光动力疗法（PDT）在疾病治疗中备受关注。然而，探索一种构建具有刺激响应性的优秀光敏剂（PSs）的新方法仍然具有挑战性。在本研究中，我们首次报道了一种新颖有效的策略，通过将供体-受体（D-A）型PSs与偶氮基团连接来促进活性氧（ROS）的生成。与没有偶氮桥连的对应物相比，偶氮桥连的PSs在I型和II型光化学反应中均表现出显著增强的ROS生成。理论计算表明，偶氮桥连导致Δ显著降低，从而通过有效的系间窜越（ISC）实现增强的ROS生成。所得的偶氮桥连PS（记为Azo-TPA-Th(+)）对临床相关耐药菌具有特别强的杀菌作用，在白光照射下杀灭效率高达99.999999%。由于偶氮桥连产生了偶氮苯结构，Azo-TPA-Th(+)在紫外光照射下可发生顺反异构化，通过关闭ISC通道形成发射性聚集体。借助未结合的Azo-TPA-Th(+)的荧光开启特性，我们提出了一种直接的方法，无需进行繁琐的平板计数测定即可直接识别有效的光动力杀菌剂量。本研究为设计具有强大ROS生成能力和刺激响应性的先进PSs开辟了一条全新的途径，在高质量PDT以及快速预测治疗效果方面具有巨大潜力。
