Lu Bingli, Wang Lingyun, Ran Xueguang, Cao Derong, Li Yifang, Zhang Xiting
Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, 381 Wushan Road, Guangzhou 510641, China.
State Key Laboratory of Swine and Poultry Breeding Industry, Key Laboratory of Animal Nutrition and Feed Science in South China, Ministry of Agriculture and Rural Affairs, Guangdong Provincial Key Laboratory of Animal Breeding and Nutrition, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, Guangzhou 510641, China.
ACS Appl Mater Interfaces. 2025 Jan 29;17(4):6040-6054. doi: 10.1021/acsami.4c19406. Epub 2025 Jan 13.
The elevated glutathione (GSH) level and hypoxia in tumor cells are two key obstacles to realizing the high performance of phototherapy. Herein, the electron-donating rotors are introduced to wings of electron-withdrawing pyrrolopyrrole cyanine (PPCy) to form donor-acceptor-donor structure -aggregates for amplified superoxide radical generation, GSH depletion, and photothermal action for hypoxic cancer phototherapy to tackle this challenge. Three PPCy photosensitizers (PPCy-H, PPCy-Br, and PPCy-TPE) produce hydroxyl radicals (•OH) and superoxide radicals (O) in hypoxia tumors exclusively as well as excellent photothermal performances under light irradiation. More importantly, GSH as an "electron reservoir" could effectively participate in photoredox processes, continuously consuming GSH and simultaneously generating more superoxide radicals. Notably, the structure-function relationship results reveal that PPCy-TPE nanoparticles (NPs) possess a high molar extinction coefficient (8.5 × 10 M cm at 778 nm) with the broadest absorption band in the near-infrared region, the most significant type I total ROS enhancement, and the highest photothermal conversion efficiency (41.3%). Furthermore, PPCy-TPE NPs have been successfully applied for and hypoxic cancer phototherapy under an 808 nm laser with outstanding specificity and biological safety. This work provides a promising single phototherapy agent against hypoxic tumors with efficient type I PDT/PTT synergistic therapy.
肿瘤细胞中升高的谷胱甘肽（GSH）水平和缺氧是实现光疗高性能的两个关键障碍。在此，将供电子转子引入吸电子吡咯并吡咯菁（PPCy）的侧翼，形成供体-受体-供体结构聚集体，用于增强超氧自由基生成、消耗GSH以及对缺氧癌症进行光热作用，以应对这一挑战。三种PPCy光敏剂（PPCy-H、PPCy-Br和PPCy-TPE）仅在缺氧肿瘤中产生羟基自由基（•OH）和超氧自由基（O），并在光照下具有优异的光热性能。更重要的是，GSH作为一种“电子库”可以有效地参与光氧化还原过程，持续消耗GSH并同时产生更多的超氧自由基。值得注意的是，结构-功能关系结果表明，PPCy-TPE纳米颗粒（NPs）在778 nm处具有高摩尔消光系数（8.5×10 M cm），在近红外区域具有最宽的吸收带、最显著的I型总ROS增强以及最高的光热转换效率（41.3%）。此外，PPCy-TPE NPs已成功应用于808 nm激光下的缺氧癌症光疗，具有出色的特异性和生物安全性。这项工作提供了一种有前景的针对缺氧肿瘤的单一光疗剂，具有高效的I型光动力疗法/光热疗法协同治疗。
