TITLE:
A Novel Therapeutic Strategy Combining Use of Intracellular Magnetic Nanoparticles under an Alternating Magnetic Field and Bleomycin
AUTHORS:
Yoshimi Inaoka, Tamami Keii, Atsushi Mimura, Kenya Murase
KEYWORDS:
Magnetic Particle Imaging (MPI), Magnetic Nanoparticles (MNPs), Hemagglutinating Virus of Japan-Envelope (HVJ-E), Intracellular Magnetic Hyperthermia, Bleomycin (BLM)
JOURNAL NAME:
Open Journal of Applied Sciences,
Vol.9 No.3,
March
13,
2019
ABSTRACT: 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 or BLM alone, and can be performed repeatedly with a
single injection of HVJ-E/MNPs.
They also suggest that
HVJ-E is effective for internalizing MNPs into cancer cells and that MPI allows
for longitudinal monitoring of the distribution of MNPs in tumors.