Kang Qiang, Liu Fen, Tan Senyou, Wu Fan, Liu Yinying, Li Zelong, Yang Sha, Huang Hejin, Xiong Jian, Chen Guodong, Wu Gui-Long, Tan Xiaofeng, Yang Qinglai
Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital & Institute of Pharmacy and Pharmacology, School of Pharmaceutical Science & NHC Key Laboratory of Birth Defect Research and Prevention & MOE Key Lab of Rare Pediatric Disease, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
Department of Radiology, The Second Affiliated Hospital, University of South China, Hengyang, Hunan 421001, China.
J Med Chem. 2025 Apr 10;68(7):7707-7719. doi: 10.1021/acs.jmedchem.5c00314. Epub 2025 Mar 26.
The advancement of mitochondria-targeted near-infrared-II (NIR-II) excitable phototheranostics constitutes a promising strategy for improving fluorescence-image-guided cancer phototherapy. However, developing phototheranostic agents that simultaneously combine high-contrast NIR-II fluorescence imaging with effective multimodal therapeutic techniques remains a substantial challenge. Herein, we reported a shielding-donor-acceptor-donor-shielding structured NIR-II phototheranostic (FCD-T) by a molecular engineering strategy, followed by self-assembly with glutathione-responsive copolymer to form FCD-T nanoparticles. The introduction of functional bithiophene endows FCD-T with significant electron-donating properties and reduces intermolecular π-π stacking interactions. The robust π-conjugation of fluorene with good rigidity would enhance the intramolecular charge transfer capability. Therefore, FCD-T NPs exhibited an NIR-II absorption peak at 1075 nm and an emission peak at 1280 nm. Upon NIR-II light excitation, such nanoparticles could generate excellent photothermal and photodynamic performances with good biocompatibility. Moreover, the NIR-II mitochondria-targeted phototherapy further facilitated mitochondrial apoptosis-related pathways, activating antitumor immunity and inhibiting tumor growth with single irradiation at low doses.
线粒体靶向近红外二区（NIR-II）可激发光诊疗技术的进步是改善荧光图像引导癌症光疗的一种有前景的策略。然而，开发同时结合高对比度NIR-II荧光成像与有效多模态治疗技术的光诊疗剂仍然是一项重大挑战。在此，我们通过分子工程策略报道了一种屏蔽-供体-受体-供体-屏蔽结构的NIR-II光诊疗剂（FCD-T），随后与谷胱甘肽响应性共聚物自组装形成FCD-T纳米颗粒。功能性联噻吩的引入赋予FCD-T显著的供电子性质并减少分子间π-π堆积相互作用。芴具有良好刚性的稳健π共轭会增强分子内电荷转移能力。因此，FCD-T纳米颗粒在1075 nm处表现出NIR-II吸收峰，在1280 nm处表现出发射峰。在NIR-II光激发下，此类纳米颗粒可产生具有良好生物相容性的优异光热和光动力性能。此外，NIR-II线粒体靶向光疗进一步促进线粒体凋亡相关途径，以低剂量单次照射激活抗肿瘤免疫并抑制肿瘤生长。
