Design of multifunctional magnetic iron oxide nanoparticles/mitoxantrone-loaded liposomes for both magnetic resonance imaging and targeted cancer therapy

Abstract

Yingna He,1 Linhua Zhang,2 Dunwan Zhu,2 Cunxian Song2 1Laboratory of Chinese Medicine Pharmacology, College of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, People’s Republic of China; 2Key Laboratory of Biomedical Material of Tianjin, Institute of Biomedical Engineering, Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, People’s Republic of China Abstract: Tumor-targeting multifunctional liposomes simultaneously loaded with magnetic iron oxide nanoparticles (MIONs) as a magnetic resonance imaging (MRI) contrast agent and anticancer drug, mitoxantrone (Mit), were developed for targeted cancer therapy and ultrasensitive MRI. The gonadorelin-functionalized MION/Mit-loaded liposome (Mit-GML) showed significantly increased uptake in luteinizing hormone–releasing hormone (LHRH) receptor overexpressing MCF-7 (Michigan Cancer Foundation-7) breast cancer cells over a gonadorelin-free MION/Mit-loaded liposome (Mit-ML) control, as well as in an LHRH receptor low-expressing Sloan-Kettering HER2 3+ Ovarian Cancer (SK-OV-3) cell control, thereby leading to high cytotoxicity against the MCF-7 human breast tumor cell line. The Mit-GML formulation was more effective and less toxic than equimolar doses of free Mit or Mit-ML in the treatment of LHRH receptors overexpressing MCF-7 breast cancer xenografts in mice. Furthermore, the Mit-GML demonstrated much higher T2 enhancement than did Mit-ML controls in vivo. Collectively, the study indicates that the integrated diagnostic and therapeutic design of Mit-GML nanomedicine potentially allows for the image-guided, target-specific treatment of cancer. Keywords: multifunctional liposome, magnetic resonance imaging, theranostic nanomedicine, mitoxantrone, gonadorelin