Assessment and comparison of magnetic nanoparticles as MRI contrast agents in a rodent model of human hepatocellular carcinoma.
The purpose of this study was to synthesize, characterize and tailor the surface properties of magnetic nanoparticles with biocompatible copolymer coatings and to evaluate the efficiency of the resulting nanoconjugates as magnetic resonance imaging (MRI) contrast agents for liver imaging. Magnetic nanoparticles with core diameters of 10 and 30 nm were synthesized by pyrolysis and were subsequently coated with a copolymer containing either carboxyl (SHP) or methoxy groups as termini. All four formulas, and ferumoxides (Feridex I.V.(®)), were individually injected intravenously into separate, normal Balb/C mice (at 2.5, 1.0 and 0.56 mg Fe kg(-1)), and the animals underwent T(2)-weighted MRI at multiple time points post injection (p.i.) to evaluate the hepatic uptake and clearance. Furthermore, we compared the abilities of the new formulas and Feridex to detect tumors in an orthotropic Huh7 tumor model. Transmission electron microscopy (TEM) revealed a narrow size distribution of both the 10 and 30 nm nanoparticles, in contrast to a wide size distribution of Feridex. MTT, apoptosis and cyclin/DNA flow cytometry assays showed that the polymer coated nanoparticles had no adverse effect on cell growth. Among all the tested formulas, including Feridex, SHP-30 showed the highest macrophage uptake at the in vitro level. In vivo MRI studies on normal mice confirmed the superiority of SHP-30 in inducing hypointensities in the liver tissue, especially at clinical dose (0.56 mg Fe kg(-1)) and 3 T field. SHP-30 showed better contrast-to-noise ratio than Feridex on the orthotropic Huh7 tumor model. SHP-30 was found to be an efficient contrast agent for liver MR imaging. The success of this study suggests that, by improving the synthetic approach and by tuning the surface properties of IONPs, one can arrive at better formulas than Feridex for clinical practice.
Department of Radiology, the Fourth Hospital of Harbin Medical University, Heilongjiang, China.
Lihong
L
Bu
Jin
J
Xie
Kai
K
Chen
Jing
J
Huang
Zoraida P
ZP
Aguilar
Andrew
A
Wang
Kin Wai
KW
Sun
Mei-Sze
MS
Chua
Samuel
S
So
Zhen
Z
Cheng
Henry S
HS
Eden
Baozhong
B
Shen
Xiaoyuan
X
Chen
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D003287:Contrast Media; D004195:Disease Models, Animal; D005290:Ferric Compounds; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000473:pathology; D008163:Luminescent Measurements; D060526:Magnetic Fields; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000633:toxicity / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D019047:Phantoms, Imaging; D011108:Polymers / Q000737:chemistry; D012377:Rodentia; D059629:Signal-To-Noise Ratio; D012995:Solubility / Q000187:drug effects; D013194:Staining and Labeling; D014867:Water / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
D003287:Contrast Media; D005290:Ferric Compounds; D058185:Magnetite Nanoparticles; D011108:Polymers; D014867:Water; C000499:ferric oxide