Iodinated Cyanine Dyes for Fast Near-Infrared-Guided Deep Tissue Synergistic Phototherapy
Iodinated Cyanine Dyes for Fast Near-Infrared-Guided Deep Tissue Synergistic Phototherapy
复制标题
用于快速近红外引导深层组织协同光疗的碘化花青染料
DOI：
10.1021/acsami.9b07694
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发表时间：
2019-07-24
影响因子：
9.5
通讯作者：
Sun, Yong
中科院分区：
文献类型：
--
作者：
Cao, Jie;Chi, Jinnan;Sun, Yong
光疗诊断学结合了深部组织成像和通过光照射进行的光疗[光动力疗法（PDT）和/或光热疗法（PTT）]，是治疗肿瘤的一种有前途的策略。近红外菁染料因其优异的物理化学性能而被广泛研究，成为光治疗诊断试剂。然而，花青染料的低单线态氧产生效率通常导致对肿瘤的治疗功效不足。本文中，我们用重原子碘修饰吲哚菁绿色衍生物Cy 7以形成新型NIR染料CyI，以改善活性氧（ROS）产生和产热，同时保持其荧光特性用于体内非侵入性成像。更重要的是，体外和体内治疗结果表明，CyI可以快速，同时产生增强的ROS和热量，诱导更多的癌细胞凋亡和更高的抑制率在深HepG 2肿瘤比其他非碘化NIR染料在NIR照射。此外，通过体内生物分布和急性毒性实验证实了碘化近红外染料的低毒性。结果表明，这种低毒的近红外染料可能是一种理想的光疗诊断剂，用于深部肿瘤治疗。我们的研究提出了一种新的方法，以实现快速协同PDT/PTT治疗深部组织。
Phototheranostics, which combines deep tissue imaging and phototherapy [photodynamic therapy (PDT) and/or photothermal therapy (PTT)] via light irradiation, is a promising strategy to treat tumors. Near-infrared (NIR) cyanine dyes are researched as potential phototheranostics reagents for their excellent photophysical properties. However, the low singlet oxygen generation efficiency of cyanine dyes often leads to inadequate therapeutic efficacy for tumors. Herein, we modified an indocyanine green derivative Cy7 with heavy atom iodine to form a novel NIR dye CyI to improve the reactive oxygen species (ROS) production and heat generation while, at the same time, maintain their fluorescence characteristics for in vivo noninvasive imaging. More importantly, in vitro and in vivo therapeutic results illustrated that CyI could quickly and simultaneously generate enhanced ROS and heat to induce more cancer cell apoptosis and higher inhibition rates in deep HepG2 tumors than other noniodinated NIR dyes upon NIR irradiation. Besides, low toxicity of the resulted iodinated NIR dyes was confirmed by in vivo biodistribution and acute toxicity. Results indicate that this low toxic NIR dye could be an ideal phototheranostics agent for deep tumor treatments. Our study presents a novel approach to achieve the fast synergistic PDT/PTT treatment in deep tissues.