荧光成像介导光动力疗法具有原位可视化、精准治疗、操作方便、无耐药性等诸多优势, 已经在癌细胞和耐药菌的成像及治疗领域展现重要的应用潜力. 光敏剂是光动力疗法的重要组成部分, 其产生的荧光强度和活性氧(ROS)效率直接影响光诊疗效果. 传统方法主要通过强化分子内电荷转移或引入重原子效应以促进系间窜越(ISC)过程,从而产生较多的三线态能量, 但严重猝灭了光敏剂的发光效率. 因此, 发展可以同时提高光敏剂荧光和 ROS 效率的分子设计方法具有重要研究意义. 本文报道了一种通过在电子给体和受体间引入不同刚性程度的稠环基元以提高分子摩尔吸光系数的策略, 不仅提高光敏剂的荧光量子效率, 同时大大提高光敏剂产生 I 和 II 型 ROS 效率. 以三苯胺作为电子给体, 吡啶盐作为电子受体, 在电子给体和受体之间分别引入苯、萘、芘稠环基元, 设计和制备了三种阳离子型光敏剂(TPA-B-PI, TPA-N-PI 和 TPA-Py-PI), 并详细研究了所制备光敏剂的光物理和光敏性能. 研究结果表明, 由于芘分子的吸光截面更大, 致使 TPA-Py-PI 具有更佳的摩尔吸光系数, 受激激发后产生更多的单线态和三线态激子, 从而表现出最佳的荧光量子效率和 I/II 型 ROS 效率. 光动力抗菌实验结果显示, 光敏剂 TPA-Py-PI 对金黄色葡萄球菌(S. aureus)、抗药性金黄色葡萄球菌(MRSA)和大肠杆菌(E. coli)均表现良好的光动力抗菌效果. 并且, TPA-Py-PI 在低浓度(25 nmol/L)和低辐照剂量(20 mW/cm2)条件下对 MRSA 实现了99.99%的抗菌效果.
Bai Xue
,
Xie Yili
,
Ma Zihang
,
Li Junyuan
,
Mo Zihua
,
Wan Qing
. 高效率阳离子型光敏剂的设计及其在低辐照剂量光动力抗菌中应用[J]. 有机化学, 0
: 202503024
-202503024
.
DOI: 10.6023/cjoc202503024
Fluorescent image-guided photodynamic therapy (PDT) has many advantages such as in situ visualization, precision treatment, easy operation, and no drug resistance, which has shown important application potential in the imaging and treatment of cancer cells and drug-resistant bacteria. Photosensitizer (PS) is an important part of PDT, and its fluorescence and reactive oxygen species (ROS) efficiency directly affect phototherapeutic effect. Traditional methods mainly enhances the intramolecular charge transfer or introduction of the heavy atom effect to promote the intersystem crossing (ISC) process to produce more triplet energy, but seriously quenching the fluorescent efficiency of the PS. Therefore, it is important to develop molecular engineering that can improve simultaneously the fluorescence and ROS efficiency of PS. This work reports a strategy to improve the molecular molar absorption coefficient by introducing fusing ring units with different rigidity between the electronic donor and acceptor, which not only improves the photoluminescence quantum efficiency, but also greatly improving the efficiency of producing type I/II ROS. Using triphenylamine as electronic donor and cationic pyridine as acceptor, three cationic PSs (TPA-B-PI, TPA-N-PI and TPA-Py-PI) with different molar absorption coefficients were designed and prepared by introducing benzene, naphthalene and pyrene rings between electronic donor and acceptor. The photophysical and photosensitive properties of the PSs were researched in detail, experimental results showed that, due to the larger absorption cross section of pyrene molecule, TPA-Py-PI had better molar absorption coefficient, and more singlet and triplet excitons were generated after excitation, resulting in the best fluorescence quantum efficiency and type I/II ROS efficiency. The results of photodynamic antibacterial experiment showed that the TPA-Py-PI had good antibacterial effect on Staphylococcus aureus (S. aureus), drug-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli). Moreover, TPA-Py-PI achieved good antibacterial efficiency of 99.99% against MRSA at low concentration (25 nmol/L) and irradiation dose (20 mW/cm2).
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