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.

肝细胞癌（HCC）是最常见的原发性肝癌类型，已成为世界上死亡率最高的恶性肿瘤之一。尽管化学疗法仍然是癌症治疗的基石，但批准用于 HCC 的化学治疗药物数量很少，因此需要新兴疗法。美拉胂醇（MEL）是一种含砷药物，已应用于晚期非洲锥虫病的治疗。在这项研究中，首次使用体外和体内研究了 MEL 治疗 HCC 的潜力实验方法。开发了一种叶酸靶向的聚乙二醇修饰的两亲性环糊精纳米颗粒，用于安全、高效和特异性地递送 MEL。因此，靶向纳米制剂在 HCC 细胞中实现了细胞特异性摄取、细胞毒性、细胞凋亡和迁移抑制。此外，靶向纳米制剂显着延长了原位肿瘤小鼠的存活时间，而不会引起毒性症状。这项研究表明靶向纳米制剂作为治疗 HCC 的新兴化疗方案的潜力。