Sui Binglin, Cheng Chen, Shi Shanshan, Wang Mingming, Xu Peisheng
Department of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, 715 Sumter St., Columbia, SC 29208, United States.
Adv Nanobiomed Res. 2021 Nov;1(11). doi: 10.1002/anbr.202100040. Epub 2021 Aug 2.
Triptolide (TPL) is a small molecule isolated from a traditional Chinese herb Tripterygium wilfordii Hook F and shows excellent anticancer effect for pancreatic cancer cells. However, the poor water solubility and severe liver toxicity of TPL hindered its clinical application. In this study, TPL was covalently conjugated to a polymer and entrapped inside the core of the TPL nanogel (nTPL) to protect it from premature leakage during blood circulation. With the help of lactobionic acid (LBA), nTPL-LBA could selectively target the tumors in an orthotopic pancreatic cancer mouse model. TPL could be subsequently released intracellularly in its original form due to the presence of elevated intracellular esterase and GSH, and eventually kills cancer cells. nTPL-LBA treatment reduced tumor burden by 99% while not introducing TPL associated liver and kidney toxicities. Most importantly, more than half of the nTPL-LBA treated animals were tumor-free, suggesting that nTPL-LBA is an effective approach in eradicating pancreatic cancer.
雷公藤甲素（TPL）是从传统中药雷公藤中分离出的一种小分子化合物，对胰腺癌细胞显示出优异的抗癌效果。然而，TPL的水溶性差和严重的肝毒性阻碍了其临床应用。在本研究中，TPL与一种聚合物共价结合，并包裹在TPL纳米凝胶（nTPL）的核心内，以防止其在血液循环中过早泄漏。在乳糖醛酸（LBA）的帮助下，nTPL-LBA可以在原位胰腺癌小鼠模型中选择性地靶向肿瘤。由于细胞内酯酶和谷胱甘肽水平升高，TPL随后可以以其原始形式在细胞内释放，并最终杀死癌细胞。nTPL-LBA治疗使肿瘤负担降低了99%，同时未引入与TPL相关的肝肾毒性。最重要的是，超过一半接受nTPL-LBA治疗的动物无肿瘤，这表明nTPL-LBA是根除胰腺癌的一种有效方法。
