Determining the Tumor Suppressive Effects of a New Drug Delivery System Loaded with Iron Oxide Nanoparticles

Nano Biomedicine
ORIGINAL ARTICLE

Determining the Tumor Suppressive Effects of a New Drug Delivery System Loaded with Iron Oxide Nanoparticles

Akiko OHKI1, 2, #, Yuhki YOKOYAMA1, #, Tomoyo YASUDA1,
Shihori KOUDA1, Satoshi SHIBATA1, Yuki SHIMOMURA1,
Xin WU1, Yoshinosuke HAMADA1, 3, 4, Seiji MORI1, 5,
Tsutomu TAKEDA1, 6, Kenya MURASE1, 2, Susumu TANAKA7, and Hirofumi YAMAMOTO1


1Department of Molecular Pathology, Osaka University Graduate School of Medicine and Health Sciences, Osaka, Japan
2Department of Medical Physics and Engineering, Osaka University Graduate School of Medicine and Health Sciences, Osaka, Japan
3Department of Health Economics and Management, Osaka University Graduate School of Medicine and Health Sciences, Osaka, Japan
4Department of Pediatric Dentistry, Osaka Dental University, Osaka, Japan
5Graduate School of Health Sciences, Morinomiya University of Medical Sciences, Osaka, Japan
6Osaka Cancer Immuno-chemotherapy Center, Osaka, Japan
7First Department of Oral and Maxillofacial Surgery, Osaka University Graduate School of Dentistry, Osaka, Japan
#These authors contributed equally to this work.



Nano Biomed 2020; 12(2):43-52, (Dec 30, Nano Biomedicine)

Synopsis
Background: Magnetic hyperthermia treatment (MHT) using magnetic nanoparticles (MNPs) has emerged as a novel strategy for cancer therapy. However, one concern of traditional hyperthermia is that it may affect both normal and tumor tissues. The current study therefore aimed to examine the antitumor effects of locally injecting magnetic nanoparticles encapsulated in super carbonate apatite (sCA), an efficient drug delivery system in combination with MHT. This study also investigated the effects of this combination on magnetic particle imaging (MPI).
Methods: First, the amount of iron encapsulated into the sCA was determined, after which a phantom experiment was performed to examine the pH sensitivity of MNPs encapsulated in the sCA (sCA-MNPs) or MNPs (pH 6.4-7.4) using an MPI scanner. Thereafter, an in vitro experiment involving the quantification of iron uptake in sCA-MNP-, MNP-, and sCA-treated Colon-26 cells and an in vivo experiment involving an MPI study after MNP or sCA-MNP injection were conducted. The antitumor effects of the following five groups were compared: Control, MNPs, MNPs + MHT, sCA-MNPs, and sCA-MNPs + MHT.
Results: Our findings showed that the maximum encapsulation efficiency of iron into the sCA was 29.5% ± 1.59%. The phantom experiment in the sCA-MNP group revealed that the MPI signal was highest during the low-pH condition and decreased during the high-pH condition. However, the MPI signal in the MNP group remained unaffected. Our results showed that sCA-MNPs were better incorporated into the cells compared to MNPs and sCA alone. The in vivo experiment showed that MPI values increased immediately after to 4 h after injection in the sCA-MNP group but did not increase in the MNPs group. The sCA-MNP + MHT group showed stronger antitumor effects compared to the MNP + MHT group 1 to 5 days after MHT.
Conclusions: Combination therapy with sCA-MNPs and MHT may be useful for cancer treatment, with sCA-MNPs being successfully imaged through MPI.


Key words: magnetic hyperthermia treatment, sCA, magnetic nanoparticles, magnetic particle imaging


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J-Stage https://www.jstage.jst.go.jp/article/nano/12/2/12_43/_article

DOI https://doi.org/10.11344/nano.12.43