Synchronously improving the photothermal conversion efficiency and photodynamic activity of organic small molecule photosensitizers is crucial for their further wide application in cancer treatment. Recently, the emerging A–D–A photosensitizer-based phototherapy systems have attracted great interest due to their plentiful inherent merits. Herein, we propose a design strategy for A–D–A photosensitizers with synchronously enhanced photothermal conversion and reactive oxygen species (ROS) generation efficiencies. Side chain programming is carried out to design three A–D–A photosensitizers (IDT-H, IDT-Br, IDT-I) containing hexyl, bromohexyl, and iodohexyl side chains, respectively. Theoretical calculations confirm that a bulky iodine atom could weaken the intermolecular π–π stacking and enhance spin–orbit coupling constants of IDT-I. These molecular mechanisms enable IDT-I nanoparticles (NPs) to exhibit 2.4-fold and 1.7-fold higher ROS generation efficiency than that of IDT-H NPs and IDT-Br NPs, respectively, as well as the highest photothermal conversion efficiency. Both the experimental results in vitro and in vivo verify that IDT-I NPs are perfectly qualified for the mission of photothermal and photodynamic synergistic therapy. Therefore, in this contribution, we provide a promising perspective for the design of A–D–A photosensitizers with simultaneously improved photothermal and photodynamic therapy ability.

中文翻译：

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侧链编程同步增强A-D-A光敏剂的光热转换效率和光动力活性


同步提高有机小分子光敏剂的光热转换效率和光动力活性对于其在癌症治疗中的进一步广泛应用至关重要。最近，新兴的基于 A-D-A 光敏剂的光疗系统因其丰富的固有优点而引起了人们的极大兴趣。在此，我们提出了一种同步增强光热转换和活性氧（ROS）生成效率的A-D-A光敏剂的设计策略。通过侧链编程设计了三种分别含有己基、溴己基和碘己基侧链的 A–D–A 光敏剂（IDT-H、IDT-Br、IDT-I）。理论计算证实，大体积的碘原子可以削弱分子间的π-π堆积并增强IDT-I的自旋轨道耦合常数。这些分子机制使IDT-I纳米粒子（NPs）的ROS生成效率分别比IDT-H NPs和IDT-Br NPs高2.4倍和1.7倍，以及最高的光热转换效率。体外和体内实验结果均证实IDT-I NPs完全胜任光热和光动力协同治疗的使命。因此，在这篇文章中，我们为同时提高光热和光动力治疗能力的 A-D-A 光敏剂的设计提供了一个有前景的前景。