Comparison of Two Ultrasmall Superparamagnetic Iron Oxides on Cytotoxicity and MR Imaging of Tumors

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Purpose: This study was performed to compare the cytotoxicity and magnetic resonance (MR) contrast in diverse cultured cells and xenograft tumors models of two ultra-small superparamagnetic iron oxides (USPIOs), thermally cross-linked superparamagnetic iron oxide nanoparticles (TCL-SPION) and monocrystalline iron oxide nanoparticles (MION-47). Materials and methods: Transmission electron microscopy (TEM) images and R(2) relaxivity values of the TCL-SPION and MION-47 were obtained and the cell viability and cell growth velocity of treated and untreated human fibroblasts and human umbilical vein endothelial cells (HUVEC) were evaluated. The effect of TCL-SPION and MION-47 on the secretion of interlukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), the production of nitric oxides and the mitochondrial membrane potentials in murine macrophage cells (RAW264.7) was compared. Human hepatocellular carcinoma cells (HepG2, 5x10(5)) were subcutaneously injected into nude mice (BALB/c) and in vivo MR imaging of tumors before and after injection with TCL-SPION or MION-47 (12.5 mg Fe/kg) was performed on a 1.5 Tesla MRI scanner. Results: On TEM images, the average core diameter of TCL-SPION was 9 nm whereas that of MION-47 was 5 nm. TCL-SPION (345.0 +/- 6.2 mM(-1)sec(-1)) had higher relaxivity (R(2)) than MION-47 (130.7 +/- 1.1 mM(-1)sec(-1)). Significant changes in cell viability and growth were not found in human fibroblasts and HUVEC exposed to TCL-SPION and MION-47. However, IL-6 and TNF-alpha secretions increased dose-dependently and significantly in the macrophages treated with MION-47 or TCL-SPION. TCL-SPION had a lower stimulatory effect on IL-6 secretions than did MION-47 (P <0.05) and nitric oxides were produced in the macrophages by MION-47 but not TCL-SPION. A change in the mitochondrial membrane potential of the macrophages was observed 24 hours after the exposure, and MION-47 induced more collapses of the mitochondrial membrane potential than did TCL-SPION. In the in vivo MR imaging, 33.0 +/- 1.3% and 7.5 +/- 0.4% signal intensity decrease on T(2)*-weighted images was observed in the tumors injected with TCL-SPION and MION-47, respectively. Conclusion: Due to the modified surface properties and larger core size of its iron oxide nanoparticles, TCL-SPION achieves lower cytotoxicity and better tumor MR contrast than MION-47. Our study suggests that TCL-SPION may be used as a new platform for tumor imaging and therapy monitoring.
Publisher
IVYSPRING INT PUBL
Issue Date
2012-01
Language
English
Article Type
Article
Keywords

CONTRAST AGENTS; PHYSICOCHEMICAL CHARACTERISTICS; BIOLOGICAL-PROPERTIES; PANCREATIC-ISLETS; CANCER-THERAPY; IN-VIVO; NANOPARTICLES; CELLS; PERMEABILITY; PLATFORM

Citation

THERANOSTICS, v.2, no.1, pp.76 - 85

ISSN
1838-7640
DOI
10.7150/thno.3462
URI
http://hdl.handle.net/10203/102208
Appears in Collection
BS-Journal Papers(저널논문)
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