Wu Kun, Liu Jiawei, Zhang Xinmin, Chao Zhicong, Fang Yanyun, Zhu Yu, Liu Yuan, Zhang Xiaobo, Wang Qi, Ju Huangxian, Liu Ying
State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University Nanjing, 210023, China.
State Key Laboratory of Organic Electronics and Information Displays & Institute of Advanced Materials (IAM), Nanjing University of Posts & Telecommunications, Nanjing, 210023, China.
Biomaterials. 2025 Apr;315:122918. doi: 10.1016/j.biomaterials.2024.122918. Epub 2024 Oct 24.
Organic near-infrared (NIR) photosensitizers (PS) largely facilitate photodynamic therapy (PDT). To overcome aggregation induced quenching and diminishment of reactive oxygen species (ROS) generation capability of NIR-PS, aggregation-induced emission (AIE) effect groups have been introduced to generate NIR AIE photosensitizers. However, currently reported NIR AIE photosensitizers all take "always-on" activity that may cause systemic phototoxic side effects. Tumor microenvironment activatable NIR AIE photosensitizers have not been reported. Here we develop an activatable NIR AIE PSnanoparticle (a-NA-PSNP) for near-infrared-II (NIR-II) fluorescence (FL) imaging-guided PDT under 808 nm excitation. NIR AIE photosensitizer (N-PS) is designed and frames with cysteine (Cys)/glutathione (GSH) responsive charge transfer complex (CTC) in bovine serum albumin (BSA) to obtain a-NA-PSNP. With the aggregated state in BSA, N-PS shows high quantum yield with good photostability. As an energy acceptor, CTC quenchs NIR-II fluorescence and ROS production capability of a-NA-PSNP in normal cells and tissues. CTC is decomposed in response to tumor microenvironment Cys/GSH, therefore recovers NIR-II fluorescence of a-NA-PSNP and efficiently generates ROS under 808 nm light irradiation. The depletion of Cys/GSH also regulates tumor intracellular reductive environment to further facilitate PDT. Both in vitro and in vivo results confirmed the tumor microenvironment selective and efficient activation of a-NA-PSNP, indicating its potential in cancer therapy.
有机近红外（NIR）光敏剂（PS）极大地推动了光动力疗法（PDT）的发展。为了克服聚集诱导猝灭以及近红外光敏剂活性氧（ROS）生成能力的降低，人们引入了聚集诱导发光（AIE）效应基团来制备近红外AIE光敏剂。然而，目前报道的近红外AIE光敏剂均具有“常开”活性，这可能会导致全身光毒性副作用。尚未有肿瘤微环境可激活的近红外AIE光敏剂的相关报道。在此，我们开发了一种可激活的近红外AIE PS纳米颗粒（a-NA-PSNP），用于在808 nm激发下进行近红外二区（NIR-II）荧光（FL）成像引导的光动力疗法。设计了近红外AIE光敏剂（N-PS），并使其与牛血清白蛋白（BSA）中半胱氨酸（Cys）/谷胱甘肽（GSH）响应性电荷转移复合物（CTC）构建框架，以获得a-NA-PSNP。在BSA中处于聚集状态时，N-PS显示出高量子产率和良好的光稳定性。作为能量受体，CTC淬灭了a-NA-PSNP在正常细胞和组织中的近红外二区荧光和ROS生成能力。CTC会响应肿瘤微环境中的Cys/GSH而分解，从而恢复a-NA-PSNP的近红外二区荧光，并在808 nm光照射下有效产生活性氧。Cys/GSH的消耗还调节肿瘤细胞内的还原环境，以进一步促进光动力疗法。体外和体内实验结果均证实了a-NA-PSNP对肿瘤微环境的选择性和高效激活，表明其在癌症治疗中的潜力。
