Yu Xinghua, Lyu Ming, Ou Xupei, Liu Wenquan, Yang Xing, Ma Xiaoxi, Zhang Tianfu, Wang Longnan, Zhang Ying-Chuan, Chen Sijie, Kwok Ryan T K, Zheng Zheng, Cui Hong-Liang, Cai Lintao, Zhang Pengfei, Tang Ben Zhong
Guangdong Key Laboratory of Nanomedicine, Shenzhen Engineering Laboratory of nanomedicine and nanoformulations, CAS-HK Joint Lab for Biomaterials, CAS Key Lab for Health Informatics, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, P. R. China.
Department of Urology & Andrology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310016, P. R. China.
Adv Healthc Mater. 2023 May;12(12):e2202907. doi: 10.1002/adhm.202202907. Epub 2023 Feb 17.
Aggregation-induced emission luminogens (AIEgens) are widely used as photosensitizers for image-guided photodynamic therapy (PDT). Due to the limited penetration depth of light in biological tissues, the treatments of deep-seated tumors by visible-light-sensitized aggregation-induced emission (AIE) photosensitizers are severely hampered. Microwave dynamic therapy attracts much attention because microwave irradiation can penetrate very deep tissues and sensitize the photosensitizers to generate reactive oxygen species (ROS). In this work, a mitochondrial-targeting AIEgen (DCPy) is integrated with living mitochondria to form a bioactive AIE nanohybrid. This nanohybrid can not only generate ROS under microwave irradiation to induce apoptosis of deep-seated cancer cells but also reprogram the metabolism pathway of cancer cells through retrieving oxidative phosphorylation (OXPHOS) instead of glycolysis to enhance the efficiency of microwave dynamic therapy. This work demonstrates an effective strategy to integrate synthetic AIEgens and natural living organelles, which would inspire more researchers to develop advanced bioactive nanohybrids for cancer synergistic therapy.
聚集诱导发光发光体（AIEgens）被广泛用作图像引导光动力疗法（PDT）的光敏剂。由于光在生物组织中的穿透深度有限，可见光敏化聚集诱导发光（AIE）光敏剂对深部肿瘤的治疗受到严重阻碍。微波动态疗法备受关注，因为微波辐射可以穿透非常深的组织并使光敏剂敏化以产生活性氧（ROS）。在这项工作中，一种靶向线粒体的AIEgen（DCPy）与活线粒体整合形成生物活性AIE纳米杂化物。这种纳米杂化物不仅可以在微波辐射下产生活性氧以诱导深部癌细胞凋亡，还可以通过恢复氧化磷酸化（OXPHOS）而非糖酵解来重新编程癌细胞的代谢途径，以提高微波动态疗法的效率。这项工作展示了一种将合成AIEgens与天然活细胞器整合的有效策略，这将激励更多研究人员开发用于癌症协同治疗的先进生物活性纳米杂化物。
