Liposomes Loaded With Hydrophobic Fe₃O₄ Nano-particles: Design And Application As A MRI Probe

Early diagnosis of tumor is essential for successful cancer therapy. For MR imaging（MRI） of tumors, MRI contrast agents have played an important role for improving the image quality by enhancing the image contrast differences between normal and diseased tissues. However, MRI contrast agents not only have special properties, but also have good biocompatibility, low toxicity and high relaxivity,so that they can be widely used in biomedical fields. Nano-magnetic liposomes（MLs）, consisting of liposomes and magnetic nanoparticles（MNPs）, have been tailored as very promising delivery vehicles in biotechnology and biomedicine applications. In many previous studies, people usually tend to research the liposome encapsulating hydrophilic nano-magnetic particles, while liposomes with hydrophobic MNPs in membrane are scarcely reported. In this paper, researches were carried out on nano-magnetic liposomes with the latter structure. The main contents are as follows:1. Hydrophobic Fe₃O₄-OA（Oleic acid） NPs have beeb synthesized by the oil-water interface method.The optimum reaction conditions are aging at 30℃ for 24 h with 6.0 M NH3.H2 O and 2.0 m L Oleic acid. The particle is uniform, with an average size of 4.3 nm and it can be dispersed stably in chloroform.2. Liposomes with hydrophobic Fe₃O₄-OA NPs in membrane were prepared by a thin film dispersing method. The optimized prescription of HMLs has been obtained by orthogonal tests in which encapsulation efficiency of Fe was used as index and phenanthroline absorption spectrophotometry was used to determine Fe content. The results showed that the best prescription preparation process of HMLs are: 1.0 mg/m L of SPC, 1.0 mg/m L of Fe content, and [SPC]:[CH] = 2-4:1（w/w）. Under these conditions, an effective Fe₃O₄ NPs loading is achieved, with encapsulation efficiency（EE%） from 91.0% to 71.0% and HMLs are spherical, with an average size of 125 nm.3. HMLs and MLs-W have been applied for in vivo T2 MR imaging of tumors, respectively. Results show that HMLs are of more advantages than MLs-W by comparing their EE% and stability. T2 relaxation time measurements demonstrate that the HMLs have r2 relaxivity of 98.50 m1s-1, much higher than MLs-W. The results of in vitro cell viability and hemolysis have revealed that the particles are quite cytocompatible and hemocompatible in the given concentration range. In vitro cell MR maging experiments using these nanoprobes further demonstrate their ability as a kind of MRI contrast. In a word, the formed HMLs can be potentially used as contrast agents for MR imaging of tumors.