Fang Laiping, Dai Jianan, Wang Xuan, Tu Yike, Li Shufang, He Kuo, Guo Wenna, Hang Lifeng, Wang Jizhuang, Diao Yanzhao, Li Wenjing, Guo Wei, Chen Ziying, Wang Jin, Li Shumei, Ma Ping'an, Jiang Guihua
Guangdong Second Provincial General Hospital, School of Medicine, Jinan University, Xingangzhong Road 466, Guangzhou, 518037, P. R. China.
College of Information Technology, Jilin Normal University, Haifeng Street 1301, Siping, 136000, P. R. China.
Small. 2025 Feb;21(6):e2409196. doi: 10.1002/smll.202409196. Epub 2025 Jan 2.
The self-assembly of hydrophobic organic phototherapeutic agents (OPTAs) with expansive planar structures into nanoparticles (NPs) represents a pivotal strategy to bolster their biocompatibility. However, the tight molecular packing within these NPs significantly influences the generation of reactive oxygen species (ROS) and the photothermal conversion efficiency (PCE), posing a substantial hurdle to elevating the efficacy of photodynamic therapy (PDT) and photothermal therapy (PTT) for such NPs. In this article, three OPTAs by donor engineering are synthesized. Notably, 4,8-Bis (5-phenylthiophen-2-yl)-6-(2-ethylhexyl)-[1,2,5] thiadiazole [3,4-F] benzotriazole (BTBT), which incorporates a benzene ring as the donor, exhibits the highest ROS generation and optimal photothermal conversion capability. To further augment the overall phototheranostic potential of BTBT NPs, a glutathione (GSH)-driven disassembly strategy is employed. This strategy not only alleviates the aggregation-caused quenching (ACQ) effect on ROS but also facilitates enhanced free molecular rotation. As a result, the ROS production sees a tenfold increase, and the photothermal conversion temperature rises by 8.3 °C, achieving a PCE of 77.03%. In summary, a versatile disassembly strategy is proposed that concurrently enhances the performance of both PDT and PTT in planar OPTAs, while also advancing the state-of-the-art in nasopharyngeal carcinoma (NPC) treatment.
具有扩展平面结构的疏水性有机光治疗剂（OPTA）自组装成纳米颗粒（NP）是增强其生物相容性的关键策略。然而，这些NP内部紧密的分子堆积显著影响活性氧（ROS）的产生和光热转换效率（PCE），对提高此类NP的光动力疗法（PDT）和光热疗法（PTT）的疗效构成了重大障碍。在本文中，通过供体工程合成了三种OPTA。值得注意的是，以苯环作为供体的4,8-双（5-苯基噻吩-2-基）-6-（2-乙基己基）-[1,2,5]噻二唑并[3,4-F]苯并三唑（BTBT）表现出最高的ROS产生量和最佳的光热转换能力。为了进一步增强BTBT NP的整体光诊疗潜力，采用了一种谷胱甘肽（GSH）驱动的拆解策略。该策略不仅减轻了对ROS的聚集诱导猝灭（ACQ）效应，还促进了自由分子旋转的增强。结果，ROS产生量增加了十倍，光热转换温度升高了8.3°C，实现了77.03%的PCE。综上所述，提出了一种通用的拆解策略，该策略同时提高了平面OPTA中PDT和PTT的性能，同时也推动了鼻咽癌（NPC）治疗的技术发展。
