Sun Zhe, Wen Haifei, Zhang Zhijun, Xu Weilin, Bao Mengni, Mo Han, Hua Xiumeng, Niu Jianlou, Song Jiangping, Kang Miaomiao, Wang Dong, Tang Ben Zhong
Pingyang Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325400, China; Shenzhen Key Laboratory of Cardiovascular Disease, Fuwai Hospital Chinese Academy of Medical Sciences, Shenzhen, 518038, China.
Center for AIE Research, College of Materials Science and Engineering, Shenzhen University, Shenzhen, 518060, China; School of Science and Engineering, Shenzhen Institute of Aggregate Science and Technology, The Chinese University of Hong Kong, Shenzhen, (CUHK-Shenzhen), Guangdong, 518172, China.
Biomaterials. 2023 Oct;301:122276. doi: 10.1016/j.biomaterials.2023.122276. Epub 2023 Aug 10.
Photoimmunotherapy has been acknowledged to be an unprecedented strategy to obtain significantly improved cancer treatment efficacy. In this regard, the exploitation of high-performance multimodal phototheranostic agents is highly desired. Apart from tailoring electron donors, acceptor engineering is gradually rising as a deliberate approach in this field. Herein, we rationally designed a family of aggregation-induced emission (AIE)-active compounds with the same donors but different acceptors based on the acceptor engineering. Through finely adjusting the functional groups on electron acceptors, the electron affinity of electron acceptors and the conformation of the compounds were simultaneously modulated. It was found that one of the molecules (named DCTIC), bearing a moderately electrophilic electron acceptor and the best planarity, exhibited optimal phototheranostic properties in terms of light-harvesting ability, fluorescence emission, reactive oxygen species (ROS) production, and photothermal performance. For the purpose of amplified therapeutic outcomes, DCTIC was fabricated into tumor and mitochondria dual-targeted DCTIC nanoparticles (NPs), which afforded good performance in the fluorescence/photoacoustic/photothermal trimodal imaging-guided photodynamic/photothermal-synergized cancer immunotherapy with the combination of programmed cell death protein-1 (PD-1) antibody. Not only the primary tumors were totally eradicated, but efficient growth inhibition of distant tumors was also realized.
光免疫疗法已被公认为是一种能显著提高癌症治疗效果的前所未有的策略。在这方面，人们迫切需要开发高性能的多模态光诊疗剂。除了定制电子供体外，受体工程作为该领域一种经过深思熟虑的方法正逐渐兴起。在此，我们基于受体工程合理设计了一系列具有相同供体但不同受体的聚集诱导发光（AIE）活性化合物。通过精细调节电子受体上的官能团，同时调节了电子受体的电子亲和力和化合物的构象。结果发现，其中一个分子（命名为DCTIC）带有中等亲电的电子受体且具有最佳平面性，在光捕获能力、荧光发射、活性氧（ROS）产生和光热性能方面表现出最佳的光诊疗性能。为了放大治疗效果，将DCTIC制备成肿瘤和线粒体双靶向的DCTIC纳米颗粒（NPs），其在荧光/光声/光热三模态成像引导的光动力/光热协同癌症免疫治疗中与程序性细胞死亡蛋白1（PD-1）抗体联合使用时表现出良好性能。不仅原发性肿瘤被完全根除，远处肿瘤的生长也得到了有效抑制。
