Preparation of Tumor-Specific Magnetoliposomes and Their Application for Hyperthermia.

Abstract

Magnetoliposomes (MLs) were conjugated with an antibody fragment to give specificity to a tumor. The antibody fragment was cross-linked to N-(6-maleimidocaproyloxy)-dipalmitoyl phosphatidylethanolamine (EMC-DPPE) in liposomal membrane. The immobilization of the antibody fragment was optimal when the content of EMC-DPPE was 10-wt% and the reaction time for immobilization was 18 h. The Fab′ fragment-conjugating MLs (FMLs) were 2.4 times higher molar immobilization density compared with the method using the whole antibody. The targetability of the FMLs to the glioma cells, U251-SP, was then investigated. The amount of FMLs uptake reached 85 pg/cell in an in vitro experiment using plastic dishes. In an in vivo experiment using glioma-harboring mice, 260 µg of the FMLs per 1 g of tumor tissue accumulated (tumor sizes was 0.1 cm 3 ), which corresponded to approximately 60% of the total injection. This value was 7 times higher than that of the MLs. After injection of the FMLs, mice were exposed to intracellular hyperthermia using the alternating magnetic field irradiation. The temperature of tumor tissue increased to 43°C and the growth of the tumor was found to be arrested over 2 weeks. These results indicate the FMLs could target the glioma cells in vitro and in vivo, and are efficiently applicable to the hyperthermia of tumor.

Heat-inducible TNF-α gene therapy combined with hyperthermia using magnetic nanoparticles as a novel tumor-targeted therapy

“…In the present study, we have used MCLs that are designed for direct injection into tumors, but we have already succeeded in the preparation of an antibody -conjugated magnetoliposome for more specific targeting and demonstrated its accumulation in tumors in vivo. 26 In either case, magnetites are heated only under AMF irradiation. Therefore, even though MCLs can leak into systemic circulation, heat is only generated where the AMF is applied.…”

Clinical applications of magnetic nanoparticles for hyperthermia

“…Other groups in Japan developed 'magnetic cationic liposomes' (MCLs) with improved adsorption and accumulation properties within tumors and demonstrated the efficacy of their technique in several animal tumor models: rat glioma [13][14][15], melanoma (in combination with immunotherapy) [16,17] and prostate cancer [18].…”

Application of hyperthermia induced by superparamagnetic iron oxide nanoparticles in glioma treatment

“…Considering the inclusion criteria, we selected 15 articles: 3 in vitro studies, [28][29][30] 10 animal model studies, 23,29,[31][32][33][34][35][36][37] and 2 clinical studies. 6,27 Although there are different centers around the world that study magnetic hyperthermia as a cancer therapy, studies of application in glioblastoma tumors are concentrated mainly in two research centers, the Department of Biotechnology, School of Engineering, Nagoya University, Japan and the Department of Radiation Medicine, University of Chariteé Medicine, Germany.…”