International Journal of Nanomedicine (Feb 2018)
Pharmacokinetics, distribution and anti-tumor efficacy of liposomal mitoxantrone modified with a luteinizing hormone-releasing hormone receptor-specific peptide
Abstract
Linhua Zhang,1 Yanqing Ren,2 Yong Wang,3 Yingna He,2 Wei Feng,2 Cunxian Song1 1Key Laboratory of Biomedical Material of Tianjin, Institute of Biomedical Engineering, Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, China; 2Hebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Disease, Pharmaceutical College, Hebei University of Chinese Medicine, Shijiazhuang City, Hebei Province, China; 3Department of Physics and Chemistry, College of Medicine, Hebei University, Baoding City, Hebei Province, China Background: A previous study developed a novel luteinizing hormone-releasing hormone (LHRH) receptor-targeted liposome. The aim of this study was to further assess the pharmacokinetics, biodistribution, and anti-tumor efficacy of LHRH receptor-targeted liposomes loaded with the anticancer drug mitoxantrone (MTO). Methods: Plasma and tissue distribution profiles of LHRH receptor-targeted MTO-loaded liposomes (LHRH-MTO-LIPs) were quantified in healthy mice or a xenograft tumor nude mouse model of MCF-7 breast cancer, and were compared with non-targeted liposomes and a free-drug solution. Results: The LHRH-MTO-LIPs demonstrated a superior pharmacokinetic profile relative to free MTO. The first target site of accumulation is the kidney, followed by the liver, and then the tumor; maximal tumor accumulation occurs at 4 h post-administration. Moreover, the LHRH-MTO-LIPs exhibited enhanced inhibition of MCF-7 breast cancer cell growth in vivo compared with non-targeted MTO-loaded liposomes (MTO-LIPs) and free MTO. Conclusion: The novel LHRH receptor-targeted liposome may become a viable platform for the future targeted treatment of cancer. Keywords: liposome, mitoxantrone, luteinizing hormone-releasing hormone receptor, tumor targeting, gonadorelin
