Delivery of melarsoprol using folate-targeted PEGylated cyclodextrin-based nanoparticles for hepatocellular carcinoma

Thumbnail Image
IJP Manuscript.pdf(1.69 MB)
Accepted Version
Li, Ya-Nan
Shi, Xiaoju
Sun, Dandan
Han, Shulan
Zou, Yifang
Wang, Lingzhi
Yang, Leilei
Li, Yutong
Shi, Ying
Guo, Jianfeng
Journal Title
Journal ISSN
Volume Title
Elsevier B.V.
Research Projects
Organizational Units
Journal Issue
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.
Liver cancer , Drug delivery , Nanoparticle , Arsenicals , Chemotherapy
Li, Y.-N., Shi, X., Sun, D., Han, S., Zou, Y., Wang, L., Yang, L., Li, Y., Shi, Y., Guo, J. and O'Driscoll, C. M. (2023) 'Delivery of melarsoprol using folate-targeted PEGylated cyclodextrin-based nanoparticles for hepatocellular carcinoma', International Journal of Pharmaceutics, 636, 122791 (8pp). doi: 10.1016/j.ijpharm.2023.122791
Link to publisher’s version