State Key Laboratory of Virology, Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (MOE), Wuhan University School of Pharmaceutical Sciences, Wuhan, 430071, China.
Hubei Province Engineering and Technology Research Center for Fluorinated Pharmaceuticals, Hubei Provincial Key Laboratory of Developmentally Originated Disease, Center for Experimental Basic Medical Education, Wuhan, 430071, China.
Adv Healthc Mater. 2018 Sep;7(18):e1800589. doi: 10.1002/adhm.201800589. Epub 2018 Jul 26.
The development of novel biodegradable and nontoxic fluorophores that integrate diagnosis and therapy for effective cancer treatment has obtained tremendous attention in the past decades. In this report, water-soluble and biocompatible small-molecule near-infrared II (NIR-II) fluorescent dye H2a-4T complexed with fetal bovine serum (FBS) and Cetuximab proteins with excellent optical properties and targeting ability is prepared. High spatial and temporal resolution imaging of hind limb vasculature and the lymphatic system of living mice using H2a-4T@FBS complex is demonstrated in precise NIR-II imaging-guided sentinel lymph node surgery. More importantly, H2a-4T@Cetuximab complex not only exhibits a remarkable cell-killing ability but also achieves highly active tumor targeting efficiency for epidermal growth factor receptor, overexpressing colorectal cancer which is beneficial to in vivo NIR-II fluorescent imaging-guided photothermal therapy of colon tumors. To the best of our knowledge, it is the first time that the concept of light-harvesting complex is exploited for enhancing the NIR-II signals and photothermal energy conversion in molecule-protein complex theranostic agent, making them a promising candidate for future clinical applications in cancer theranostics.
在过去的几十年中,开发新型可生物降解和无毒的荧光团,将诊断和治疗集成在一起,以实现有效的癌症治疗,引起了人们的极大关注。在本报告中,制备了水溶性和生物相容性的小分子近红外二区(NIR-II)荧光染料 H2a-4T 与胎牛血清(FBS)和西妥昔单抗的复合物,具有优异的光学性能和靶向能力。使用 H2a-4T@FBS 复合物对活体小鼠的后肢血管和淋巴管进行了高时空分辨率成像,实现了精确的 NIR-II 成像引导前哨淋巴结手术。更重要的是,H2a-4T@Cetuximab 复合物不仅表现出显著的细胞杀伤能力,而且对表皮生长因子受体(过度表达于结直肠癌)具有高靶向效率,有利于体内 NIR-II 荧光成像引导的光热治疗结肠肿瘤。据我们所知,这是首次利用光收集复合物来增强分子-蛋白复合物治疗剂中的 NIR-II 信号和光热能量转换,使其成为癌症治疗中具有广阔应用前景的候选者。