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

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Document pages: 17 pages

Abstract: Purpose: The purpose of this study was to present a novel therapeutic strategy combining use ofintracellular magnetic nanoparticles (MNPs) under an alternating magnetic field(AMF) and bleomycin (BLM), and to evaluate its therapeutic effect usingtumor-bearing mice. Materialsand Methods: MNPs (Resovist?, 1.05 mg iron) wereincorporated 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-bearingmice 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. TheAMF was applied to the mice one hour after the injection of agents (AMFtreatment). The mice injected with HVJ-E MNPs were imaged using our magneticparticle imaging (MPI) scanner immediately (13 min) before, immediately (22min) after, and 3, 7, and 14 days after the injection of agents, and thetemporal changes of the average and maximum MPI pixel values in the tumor werequantitatively evaluated. The therapeutic effect was evaluated by calculatingthe 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 distributionof 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 daysafter AMF treatment. The average and maximum MPI pixel values in the tumor were almost constant for 14days. TEM observation confirmed that most of the HVJ-E MNPs wereinternalized into tumor cells within one hour after injection. Conclusion: A novel therapeuticstrategy with use of AMF treatment and BLM was presented, and thetime-dependent change of MNPs in tumors was evaluated using MPI. The present resultssuggest that this novel strategy can suppress tumor volume growth over AMFtreatment or BLM alone, and can be performed repeatedly with asingle injection of HVJ-E MNPs.They also suggest thatHVJ-E is effective for internalizing MNPs into cancer cells and that MPI allowsfor longitudinal monitoring of the distribution of MNPs in tumors.

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