Delivery of triptolide with reduction-sensitive polymer nanoparticles for liver cancer therapy on patient-derived xenografts models
Delivery of triptolide with reduction-sensitive polymer nanoparticles for liver cancer therapy on patient-derived xenografts models
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DOI：
10.1016/j.cclet.2020.05.034
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发表时间：
2020-12-01
影响因子：
9.1
通讯作者：
Li, Aimin
中科院分区：
文献类型：
--
作者：
He, Mengxue;Yu, Ling;Li, Aimin
肝细胞癌已成为全球第四大癌症相关死亡原因，由于耐药和毒副作用大，对化疗和手术治疗的反应较差，因此仍是预后最差的疾病之一。雷公藤甲素(TP)是中草药中的关键成分，几个世纪以来一直被用于治疗炎症和抗肿瘤。然而，在过去的二十年里，由于患者的严重全身毒性和低水溶性以及高毒性，对这种强效药物的研究只取得了有限的成功。在此，我们报道了一种为谷胱甘肽(GSH)引发的药物释放而开发的用于癌症治疗的还原响应型药物递送系统。GSH敏感的TP纳米粒显著增加了肿瘤的蓄积，改善了动物体内的药物毒性，这可能是由于活性TP在癌细胞内的持续逐步释放所致。此外，在患者来源的肝癌异种移植模型中，与给予游离TP相比，给予雷公藤甲素纳米粒可增强抗肿瘤效果。这些发现表明，GSH敏感的TP释放可能是一种有前途的癌症治疗策略。(C)2020年中国医学科学院中国化学会、药物所。爱思唯尔出版，版权所有。
Hepatocellular carcinoma (HCC) has become the fourth predominant cause of cancer-related deaths worldwide, and HCC is still one of the worst prognoses for survival as it is poorly responsive to both chemotherapy and surgical treatment due to drug resistance and great toxic effects. Triptolide (TP), a key ingredient from the traditional Chinese medical herb, has been utilized to treat inflammation and antitumor for centuries. However, investigations of this potent agent have been met with only limited success due to the severe systemic toxicities in patients and low water solubility as well as its high toxicity over the past two decades. Herein, we reported the development of a reduction-responsive drug delivery system loaded with TP for glutathione (GSH)-triggered drug release for cancer therapy. With the GSH-sensitive TP loaded nanoparticles, the remarkable increases in tumor accumulation and amelioration of drug toxicity in animals are demonstrated, which is likely due to sustained stepwise release of active TP within cancer cells. Moreover, in a patient-derived tumor xenograft model of liver cancer, administration of tritolide nanoparticles enhances the antitumor efficacy relative to administration of free TP. These findings indicate that GSH-sensitive release of TP may be a promising strategy for cancer treatment. (C) 2020 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.