Mediated Imaging and Improved Targeting of Farnesylthiosalicylic Acid Delivery for Pancreatic Cancer via Conjugation with Near-Infrared Fluorescence Heptamethine Carbocyanine Dye
Mediated Imaging and Improved Targeting of Farnesylthiosalicylic Acid Delivery for Pancreatic Cancer via Conjugation with Near-Infrared Fluorescence Heptamethine Carbocyanine Dye
复制标题
通过与近红外荧光七次甲基羰花青染料结合介导成像并改善胰腺癌法尼基硫代水杨酸递送的靶向性
DOI：
10.1021/acsabm.9b01068
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发表时间：
2020
影响因子：
4.7
通讯作者：
Changhong Shi
中科院分区：
文献类型：
--
作者：
Ya Zhao;He Zhang;Pengpeng Wu;Dengxu Tan;Yong Zhao;Caiqin Zhang;Jie Wang;Bing Bai;Jiaze An;Changhong Shi
S-反式-反式-法尼基硫代水杨酸（FTS）是一种Ras抑制剂，具有理想的抗癌特性，目前正在进行胰腺癌（PC）的临床试验。然而，其水溶性差和生物利用度低，严重阻碍了其临床应用。提高FTS生物利用度的策略是开发合适的药物递送方法。在这里，我们使用近红外荧光（NIRF）七甲川碳菁（HC）染料与FTS共轭（产生FTS-148）作为药物递送系统，以提高FTS的生物利用度。我们进一步研究其肿瘤靶向功能。FTS-148具有较好的生物利用度和生物物理学特性，对癌细胞具有选择性识别。FTS-148显著降低PC细胞增殖，并且在细胞来源的异种移植物（CDX）模型和患者来源的肿瘤异种移植物（PDX）模型中在限制肿瘤生长方面比FTS更有效。FTS-148可以特异性识别小鼠皮下模型或兔原位模型中的PC细胞，并允许通过NIRF光学成像实时监测治疗效果。FTS-148处理显著降低PC细胞中Ras表达并增加肿瘤组织凋亡。总之，FTS与HC染料偶联后具有更高的生物利用度和肿瘤靶向性。它为PC的成像和治疗提供了一种潜在的药物。
S-trans–trans-Farnesylthiosalicylic acid (FTS) is a Ras inhibitor that exhibits desirable anticancer property and currently undergoing clinical trials for pancreatic cancer (PC). However, its poor water solubility and low bioavailability have severely hampered clinical applications. A strategy to improve FTS bioavailability is to develop a suitable drug delivery method. Here, we use a near-infrared fluorescence (NIRF) heptamethine carbocyanine (HC) dye conjugated with FTS (to produce FTS-148) as a drug delivery system to enhance FTS bioavailability. We further investigate its tumor-targeting functions. FTS-148 displayed better bioavailability and photophysical property and selective recognition of cancer cells. FTS-148 significantly reduced PC cell proliferation, and more effective than FTS in restricting tumor growth both in a cell-derived xenograft (CDX) model and a patient-derived tumor xenograft (PDX) model. FTS-148 can specifically recognize PC cells in mice subcutaneous models or rabbit orthotopic models and allows real-time monitoring of the therapeutic effects by NIRF optical imaging. FTS-148 treatment significantly reduced Ras expression in PC cells and increased tumor tissue apoptosis. In short, FTS conjugated with HC dye had enhanced bioavailability and tumor-targeting property. It provides a potential agent for imaging and therapy of PC.