A Novel Therapeutic Strategy Combining Use of Intracellular Magnetic Nanoparticles under an Alternating Magnetic Field and Bleomycin

• 作者: Atsushi Mimura Kenya Murase Tamami Keii Yoshimi Inaoka
• 来源期刊: 应用科学(英文)
• 学科: 医学
• 关键词: MAGNETIC Particle Imaging (MPI) MAGNETIC Nanoparticles (MNPs) Hemagglutinating Virus of Japan-Envelope (HVJ-E) INTRACELLULAR MAGNETIC HYPERTHERMIA BLEOMYCIN (BLM)
• 年，卷（期）: 2019,（3）
• 页码范围: 87-103
• 页数: 17页
• 分类号: R73

摘要

Purpose: The purpose of this study was to present a novel therapeutic strategy combining use of intracellular magnetic nanoparticles (MNPs) under an alternating magnetic field (AMF) and bleomycin (BLM), and to evaluate its therapeutic effect using tumor-bearing mice. Materials and Methods: MNPs (Resovist?, 1.05 mg iron) were incorporated into the hemagglutinating virus of Japan-envelope (HVJ-E) vector (~5 × 109 particles) (HVJ-E/MNPs) by centrifugation at 10,000 × g for 5 min at 4°C. Tumor-bearing mice were prepared by inoculating Colon-26 cells subcutaneously into the backs of BALB/c mice. When the tumor volume reached ~100 mm3, HVJ-E/MNPs and/or BLM were injected directly into the tumor. The AMF was applied to the mice one hour after the injection of agents (AMF treatment). The mice injected with HVJ-E/MNPs were imaged using our magnetic particle imaging (MPI) scanner immediately (13 min) before, immediately (22 min) after, and 3, 7, and 14 days after the injection of agents, and the temporal changes of the average and maximum MPI pixel values in the tumor were quantitatively evaluated. The therapeutic effect was evaluated by calculating the relative tumor volume growth (RTVG) from the tumor volumes measured each day. Transmission electron microscopic (TEM) observation of resected tumors was also performed to confirm the intracellular distribution of MNPs. Results: The AMF treatment combined with BLM significantly decreased the RTVG value compared with AMF treatment alone at 9 to 14 days, and BLM alone at 3 to 5 days after AMF treatment. The average and maximum MPI pixel values in the tumor were almost constant for 14 days. TEM observation confirmed that most of the HVJ-E/MNPs were internalized into tumor cells within one hour after injection. Conclusion: A novel therapeutic strategy with use of AMF treatment and BLM was presented, and the time-dependent change of MNPs in tumors was evaluated using MPI. The present results suggest that this novel strategy can suppress tumor volume growth over AMF treatment o