Zhao Xiujie, Zhao Hongjie, Wang Shuo, Fan Zhiwen, Ma Yan, Yin Yongmei, Wang Wei, Xi Rimo, Meng Meng
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and KLMDASR of Tianjin, Nankai University, Tongyan Road, Haihe Education Park, Tianjin 300350, China.
Institute of Chemistry & Center for Pharmacy, University of Bergen, Bergen 5020, Norway.
J Am Chem Soc. 2021 Dec 15;143(49):20828-20836. doi: 10.1021/jacs.1c09155. Epub 2021 Dec 3.
In recent years, cancer phototherapy has been extensively studied as noninvasive cancer treatment. To present efficient recognition toward cancer cells, most photosensitizers (PSs) are required to couple with tumor-targeted ligands. Interestingly, the heptamethine cyanine IR780 displays an intrinsic tumor-targeted feature even without modification. However, the photothermal efficacy and photostability of IR780 are not sufficient enough for clinical use. Herein, we involve a twisted structure of tetraphenylethene (TPE) between two molecules of IR780 to improve the photothermal conversion efficiency (PCE). The obtained molecule T780T shows strong near-infrared (NIR) fluorescence and improved PCE (38.5%) in the dispersed state. Also, the photothermal stability and ROS generation capability of T780T at the NIR range (808 nm) are both promoted. In the aqueous phase, the T780T was formulated into uniform nanoaggregates (∼200 nm) with extremely low fluorescence and PTT response, which would reduce in vivo imaging background and side effect of PTT response in normal tissues. After intravenous injection into tumor-bearing mice, the T780T nanoaggregates display high tumor accumulation and thus remarkably inhibit the tumor growth. Moreover, the enhanced photostability of the T780T allows for twice irradiation after one injection and leads to more significant tumor inhibition. In summary, our study presents a tumor-targeted small-molecule PS for efficient cancer therapy and brings a new design of heptamethine cyanine PS for potential clinical applications.
近年来，癌症光疗作为一种非侵入性癌症治疗方法得到了广泛研究。为了实现对癌细胞的高效识别，大多数光敏剂（PSs）需要与肿瘤靶向配体偶联。有趣的是，七甲川花菁IR780即使未经修饰也具有内在的肿瘤靶向特性。然而，IR780的光热疗效和光稳定性不足以满足临床应用需求。在此，我们在两个IR780分子之间引入扭曲的四苯乙烯（TPE）结构，以提高光热转换效率（PCE）。所得到的分子T780T在分散状态下表现出强烈的近红外（NIR）荧光并提高了PCE（38.5%）。此外，T780T在近红外范围（808 nm）的光热稳定性和活性氧生成能力均得到提升。在水相中，T780T被制备成均匀的纳米聚集体（约200 nm），具有极低的荧光和光热治疗（PTT）响应，这将减少体内成像背景以及正常组织中PTT响应的副作用。将T780T纳米聚集体静脉注射到荷瘤小鼠体内后，其显示出高肿瘤蓄积，并因此显著抑制肿瘤生长。此外，T780T增强的光稳定性使得一次注射后可进行两次照射，并导致更显著的肿瘤抑制效果。总之，我们的研究提出了一种用于高效癌症治疗的肿瘤靶向小分子PS，并为潜在的临床应用带来了一种新型的七甲川花菁PS设计。
