Abstract：
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, and has become one of the most lethal malignancies in the world. Although chemotherapy remains a cornerstone of cancer therapy, the number of chemotherapeutic drugs approved for HCC is low, and emerging therapeutics are needed. Melarsoprol (MEL) is an arsenic-containing drug, and has been applied in the treatment of human African trypanosomiasis at the late stage. In this study, the potential of MEL for HCC therapy was investigated for the first time using in vitro and in vivo experimental approaches. A folate-targeted polyethylene glycol-modified amphiphilic cyclodextrin nanoparticle was developed for safe, efficient and specific delivery of MEL. Consequently, the targeted nanoformulation achieved cell-specific uptake, cytotoxicity, apoptosis and migration inhibition in HCC cells. Furthermore, the targeted nanoformulation significantly prolonged the survival of mice with orthotopic tumor, without causing toxic signs. This study indicates the potential of the targeted nanoformulation as an emerging chemotherapy option for treating HCC.
摘要：
肝细胞癌(HCC)是原发性肝癌最常见的类型,已经成为世界上最致命的恶性肿瘤之一。虽然化疗仍然是癌症治疗的基石，批准用于肝癌的化疗药物数量很少，需要新兴的治疗方法。美乐索洛尔（MEL）是一种含砷药物，并已应用于晚期人类非洲锥虫病的治疗。在这项研究中,首次使用体外和体内实验方法研究了MEL用于HCC治疗的潜力。开发了一种叶酸靶向聚乙二醇修饰的两亲性环糊精纳米颗粒，高效和具体的MEL交付。因此,靶向纳米制剂实现了细胞特异性摄取，细胞毒性，肝癌细胞凋亡和迁移抑制。此外，靶向纳米制剂可显着延长原位肿瘤小鼠的生存期，不会造成有毒迹象。这项研究表明靶向纳米制剂作为治疗HCC的新兴化疗选择的潜力。
