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Facile synthesis of ultrasmall PEGylated iron oxide nanoparticles for dual-contrast T1- and T2weighted magnetic resonance imaging
This article has been downloaded from IOPscience. Please scroll down to see the full text article. 2011 Nanotechnology 22 245604 (http://iopscience.iop.org/0957-4484/22/24/245604) View the table of contents for this issue, or go to the journal homepage for more
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IOP PUBLISHING
NANOTECHNOLOGY
Nanotechnology 22 (2011) 245604 (7pp)
doi:10.1088/0957-4484/22/24/245604
Facile synthesis of ultrasmall PEGylated iron oxide nanoparticles for dual-contrast T1- and T2-weighted magnetic resonance imaging Fengqin Hu1,3 , Qiaojuan Jia2 , Yilin Li2 and Mingyuan Gao2 1
College of Chemistry, Beijing Normal University, Beijing 100875, People’s Republic of China 2 Institute of Chemistry, CAS, Bei Yi Jie 2, Beijing 100190, People’s Republic of China E-mail:
[email protected]
Received 7 January 2011, in final form 14 March 2011 Published 21 April 2011 Online at stacks.iop.org/Nano/22/245604 Abstract The development of new types of high-performance nanoparticulate MR contrast agents with either positive (T1 ) or dual-contrast (both positive and negative, T1 + T2 ) ability is of great importance. Here we report a facile synthesis of ultrasmall PEGylated iron oxide nanoparticles for dual-contrast T1 - and T2 -weighted MRI. The produced superparamagnetic iron oxide nanoparticles (SPIONs) are of high crystallinity and size uniformity with an average diameter of 5.4 nm, and can be individually dispersed in the physiological buffer with high stability. The SPIONs reveal an impressive saturation magnetization of 94 emu g−1 Fe3 O4 , the highest r1 of 19.7 mM−1 s−1 and the lowest r2 /r1 ratio of 2.0 at 1.5 T reported so far for PEGylated iron oxide nanoparticles. T1 - and T2 -weighted MR images showed that the SPIONs could not only improve surrounding water proton signals in the T1 -weighted image, but induce significant signal reduction in the T2 -weighted image. The good contrast effect of the SPIONs as T1 + T2 dual-contrast agents might be due to its high magnetization, optimal nanoparticle size for T1 + T2 dual-contrast agents, high size monodispersity and excellent colloidal stability. In vitro cell experiments showed that the SPIONs have little effect on HeLa cell viability. S Online supplementary data available from stacks.iop.org/Nano/22/245604/mmedia
unpaired electrons) and Mn2+ (five unpaired electrons) chelates, which are positive (T1 ) contrast agents [5–7]. Their relaxivity ratio r2 /r1 is commonly in the range of 1–2. Areas enriched with paramagnetic molecular complexes exhibit an increase in signal intensity and appear bright in T1 -weighted images [1, 5]. This kind of contrast agent is limited by their nonspecificity to target, quick removal by renal excretion and short accumulation time in practical applications [8]. Superparamagnetic nanoparticles (typically iron oxide nanoparticles) are another class of MR contrast agents that was normally used as negative (T2 ) contrast agents. The nanoparticles commonly show a high r2 /r1 ratio of at least 10, produce a decrease in signal intensity and appear dark in T2 -weighted images [9–16]. Compared with the conventional paramagnetic agents, nanoparticle-based contrast agents have
1. Introduction Magnetic resonance imaging (MRI) is currently one of the most powerful tools for biological molecular imaging and clinical diagnosis [1–4]. One of the significant advantages of MRI is the ability to acquire three-dimensional tomographic information of whole tissue samples and animals with high spatial resolution and soft tissue contrast. In addition, images are acquired without the use of ionizing radiation or radiotracers. Medical diagnosis requires enhanced contrast between normal and pathological tissues, resulting in the development of exogenous MR contrast agents. Most of the presently commercial MR contrast agents are paramagnetic molecular complexes, such as Gd3+ (seven 3 Author to whom any correspondence should be addressed.
0957-4484/11/245604+07$33.00
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© 2011 IOP Publishing Ltd Printed in the UK & the USA
Nanotechnology 22 (2011) 245604
F Hu et al
through decomposition of Fe(acac)3 in triethylene glycol (TREG) in the presence of HOOC–PEG–COOH via a onepot reaction. The produced SPIONs show excellent colloidal stability in the physiological buffer, present an impressive saturation magnetization of 94 emu g−1 Fe3 O4 and a r1 of 19.7 mM−1 s−1 as well as a r2 /r1 ratio of 2.0 at 1.5 T. To the best of our knowledge, these are the highest r1 and lowest r2 /r1 ratio at 1.5 T reported so far for PEGylated iron oxide nanoparticles, indicating that the SPIONs are promising T1 +T2 dual-contrast agents for a variety of MRI applications.
a number of advantages due to its nanoparticulate structures: (1) the magnetic properties of the agents can be tailored by size, shape, composition and assembly; (2) the nanoparticulate agents show tunable cellular uptake; (3) the agents have large specific surface areas that facilitate conjugation with targeting molecules and other probes for achieving targeting and multimodal agents and (4) the nanoscale dimension, adjustable surface structure and shape of the agents allow varying and favorable biodistribution. Nevertheless, a negative contrast effect and magnetic susceptibility artifacts are key factors that restrict the applications of superparamagnetic nanoparticles in MRI. The resulting dark signal might mislead the clinical diagnosis in T2 -weighted MRI because the signal is often confused with the signals from bleeding, calcification or metal deposits, and the susceptibility artifacts distort the background image [17, 18]. Therefore, the development of new types of nanoparticulate MR contrast agents with either T1 or T1 + T2 dual-contrast ability is urgently needed. For the above reasons, nanoparticles of Gd2 O3 [19–22], GdF3 [23], GdPO4 [24] and MnO [18] have been investigated as T1 MR contrast agents in the past few years. However, the sophisticated synthesis procedures and low r1 values make them far from optimal for positive MRI. Recently, superparamagnetic iron oxide nanoparticles with ultrasmall sizes (90% at all Fe incubation concentrations. These results demonstrate that the SPIONs show little cytotoxicity, indicating that they have potential in in vivo MRI applications.
4. Conclusions In summary, a facile one-pot reaction was developed to synthesize 5.4 nm water-soluble PEG-coated SPIONs which can act as high-performance T1 + T2 dual MR contrast agents. The SPIONs produced with this procedure are highly crystalline, superparamagnetic at room temperature, and can be individually dispersed in the physiological buffer with high stability. The SPIONs present an impressive saturation magnetization value of 94 emu g−1 Fe3 O4 and a r1 of 19.7 mM−1 s−1 as well as a r2 /r1 ratio of 2.0 at 1.5 T. T1 and T2 -weighted MR images demonstrated that the SPIONs could be utilized as high-performance T1 + T2 dual-contrast agents. High magnetization, optimal nanoparticle size for T1 + T2 dual-contrast agents, high size monodispersity and excellent colloidal stability might be factors for the good contrast effect of the SPIONs as T1 + T2 dual-contrast agents. The cell viability assay showed that the SPIONs have little effect on HeLa cell viability. The novel SPIONs should have great potential in dual-contrast T1 - and T2 -weighted MRI for molecular imaging and diagnostic applications. 6
Nanotechnology 22 (2011) 245604
F Hu et al
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