Lim Wonbong, Byun Jae Yong, Jo Gayoung, Kim Eun Jeong, Park Min Ho, Hyun Hoon
Department of Premedical Program, School of Medicine, Chosun University, Gwangju 61452, Korea.
Madisarang Hospital, Cheongju 61469, Korea.
Pharmaceutics. 2022 Mar 19;14(3):676. doi: 10.3390/pharmaceutics14030676.
A tumor-targeted near-infrared (NIR) fluorophore CA800Cl was developed based on commercially available IR-786 by modulating its physicochemical properties. IR-786, a hydrophobic cationic heptamethine cyanine fluorophore, was previously recognized as a mitochondria-targeting NIR agent with excellent optical properties. Owing to the poor tumor specificity of IR-786 itself, in vivo studies on tumor-targeted imaging have not yet been investigated. A chloro-cyclohexene ring and indolium side groups on the heptamethine chain are key structural features that improve tumor targetability, owing to better biodistribution and clearance. Thus, IR-786 should be designed to be more soluble in aqueous solutions so that it can preferentially accumulate in the tumor based on the structure-inherent targeting strategy. In this study, we developed a bifunctional NIR fluorophore CA800Cl by incorporating carboxylate moieties in the basic structure of IR-786. This improved its tumor targetability and water solubility, thereby enabling the use of CA800Cl for enhanced photothermal cancer therapy.
基于市售的IR-786，通过调节其物理化学性质，开发了一种肿瘤靶向近红外（NIR）荧光团CA800Cl。IR-786是一种疏水性阳离子七甲川花菁荧光团，此前被认为是一种具有优异光学性质的线粒体靶向近红外试剂。由于IR-786本身的肿瘤特异性较差，尚未对其进行肿瘤靶向成像的体内研究。七甲川链上的氯代环己烯环和吲哚侧基是改善肿瘤靶向性的关键结构特征，这得益于更好的生物分布和清除率。因此，应将IR-786设计成在水溶液中更易溶解，以便它能够基于结构固有靶向策略优先在肿瘤中积累。在本研究中，我们通过在IR-786的基本结构中引入羧基部分，开发了一种双功能近红外荧光团CA800Cl。这提高了其肿瘤靶向性和水溶性，从而使CA800Cl能够用于增强型光热癌症治疗。
