Polymer-brush-afforded SPIO Nanoparticles Show a Unique Biodistribution and MR Imaging Contrast in Mouse Organs

Ting Chen; Yuki Mori; Chizuko Inui-Yamamoto; Yutaka Komai; Yoshiyuki Tago; Shinichi Yoshida; Yoshitsugu Takabatake; Yoshitaka Isaka; Kohji Ohno; Yoshichika Yoshioka

doi:10.2463/mrms.mp.2016-0067

Polymer-brush-afforded SPIO Nanoparticles Show a Unique Biodistribution and MR Imaging Contrast in Mouse Organs

Magn Reson Med Sci. 2017 Oct 10;16(4):275-283. doi: 10.2463/mrms.mp.2016-0067. Epub 2017 Jan 30.

Authors

Ting Chen^{1

2}, Yuki Mori^{1

2}, Chizuko Inui-Yamamoto^{1

2}, Yutaka Komai¹, Yoshiyuki Tago³, Shinichi Yoshida³, Yoshitsugu Takabatake⁴, Yoshitaka Isaka⁴, Kohji Ohno⁵, Yoshichika Yoshioka^{1

2}

Affiliations

¹ Biofunctional Imaging Laboratory, WPI Immunology Frontier Research Center (WPI IFReC), Osaka University.
² Functional Imaging Technology, Center for Information and Neural Networks (CiNet), National Institute of Information and Communications Technology (NICT) and Osaka University.
³ Biotechnology Development Laboratories, Kaneka Corporation.
⁴ Department of Nephrology, Osaka University Graduate School of Medicine.
⁵ Institute for Chemical Research, Kyoto University.

Abstract

Introduction: To investigate the biodistribution and retention properties of the new super paramagnetic iron oxide (new SPIO: mean hydrodynamic diameter, 100 nm) nanoparticles, which have concentrated polymer brushes in the outer shell and are difficult for phagocytes to absorb, and to compare the new SPIO with clinically approved SPIO (Resovist: mean hydrodynamic diameter, 57 nm).

Materials and methods: 16 male C57BL/6N mice were divided in two groups according to the administered SPIO (n = 8 for each group; intravenous injection does, 0.1 ml). In vivo magnetic resonance imaging (MRI) was performed before and one hour, one day, one week and four weeks after SPIO administration by two dimensional-the fast low angle shot (2D-FLASH) sequence at 11.7T. Ex vivo high-resolution images of fixed organs were also obtained by (2D-FLASH). After the ex vivo MRI, organs were sectioned and evaluated histologically to confirm the biodistribution of each particle precisely.

Results: The new SPIO was taken up in small amounts by liver Kupffer cells and showed a unique in vivo MRI contrast pattern in the kidneys, where the signal intensity decreased substantially in the boundaries between cortex and outer medulla and between outer and inner medulla. We found many round dark spots in the cortex by ex vivo MRI in both groups. Resovist could be detected almost in the cortex. The shapes of the dark spots were similar to those observed in the new SPIO group. Transmission electron microscopy revealed that Resovist and the new SPIO accumulated in different cells of glomeruli, that is, endothelial and mesangial cells, respectively.

Conclusion: The new SPIO was taken up in small amounts by liver tissue and showed a unique MRI contrast pattern in the kidney. The SPIO were found in the mesangial cells of renal corpuscles. Our results indicate that the new SPIO may be potentially be used as a new contrast agent for evaluation of kidney function as well as immunune function.

Keywords: kidney; magnetic resonance imaging; mouse; stealth probe; super paramagnetic iron oxide.

MeSH terms

Animals
Contrast Media / administration & dosage*
Ferric Compounds / administration & dosage*
Injections, Intravenous
Kidney / diagnostic imaging*
Liver / diagnostic imaging*
Magnetic Resonance Imaging / methods*
Male
Mice
Mice, Inbred C57BL
Nanoparticles / administration & dosage*
Polymers / administration & dosage*
Tissue Distribution

Substances

Contrast Media
Ferric Compounds
Polymers
ferric oxide