Article pubs.acs.org/JPCC
Facile and Green Synthesis of Biocompatible and Bioconjugatable Magnetite Nanofluids for High-Resolution T2 MRI Contrast Agents Sheng Huang, Wei Yan, Gaofei Hu, and Leyu Wang* State Key Laboratory of Chemical Resource Engineering, School of Science, Beijing University of Chemical Technology, Beijing 100029, Peoples Republic China S Supporting Information *
ABSTRACT: By using water as an exclusive solvent, a facile one-pot strategy was developed for the preparation of hydrophilic magnetite nanofluids coated with oxidized dextran. These as-synthesized magnetic nanofluids are highly watersoluble, biocompatible, and bioconjugatible for targeted detection because of the enriched carboxylate groups in the oxidized dextran shell. These nanoparticles are less than 10 nm and demonstrate strong magnetization, low cytotoxicity, and high T2-weighted MR image signal intensity (r2 = 250.5 mM−1 s−1, 3.7 times larger than the commercial product). Also, these magnetic nanofluids are highly stable in many kinds of aqueous media; even though a strong magnet is adjoined to the nanofluids, the whole colloid solution rather than the solid particle only is drawn to the side wall of the vial. These novel properties render this magnetic nanofluid desirable for wide bioapplications including MRI, highly efficient magnetic bioseparation, targeted drug delivery, and magnetic hyperthermia.
■
INTRODUCTION The in vitro and in vivo application of nanomaterials as diagnostic and therapeutic agents is of intense interest owing to their unique optical, electrical, and magnetic properties.1−12 One of the most rapidly developing and exciting applications of nanomaterials in biomedical fields is the use of magnetic nanomaterials for magnetic resonance imaging (MRI), controlled drug delivery and magnetic bioseparation.13−16 Kauzlarich and co-workers developed Mn-doped quantum dots (QDs) and Fe/Au alloy nanoparticles as T1-weighted contrast agents. Especially, the Mn-doped QDs are multifunctional imaging agents for both fluorescence and MRI applications. During the past decades, many types of magnetic nanoparticles coated with oleic acid or oleylamine were successfully prepared via the pyrolysis methods, but they were not water-soluble, and thus were unsuitable for bioapplications before surface modification.17−23 Li’s group and Ge developed facile strategies to prepare magnetic nanomaterials with hydrophilic surfaces in water or ethylene glycol solution.24−27 However, biomedical applications of the inorganic nanomaterials have been impeded owing to concerns regarding the water dispersibility, biocompatibility, and bioconjugatability. Therefore, it remains a challenge, using nontoxic and inexpensive chemicals, to prepare magnetite nanomaterials with small particle size, high transverse relaxivity (r2),28−30 and thin coating shell to render them water dispersible, biocompatible, bioconjugatable, and especially stable in many kinds of aqueous media like a nanofluid. Dextran has already been proven to be nontoxic, watersoluble, biocompatible, and biodegradable, and has been used for surface functionalization of magnetic nanoparticles.31,32 To © 2012 American Chemical Society
obtain the aldehyde groups for bioconjugation, the dextran on the NPs was further oxidized by sodium periodate (NaIO4) after the formation of dextran-coated NPs.32 In most cases of Fe3O4@dextran NPs, the particles were prepared by the coprecipitating Fe2+ and Fe3+ cations using ammonia or NaOH aqueous solution at a relatively low temperature (≤80 °C), which required careful adjustment of pH value to control the particle size and size distribution. Still, the size distribution of the obtained NPs was still pretty broad due to the weak binding of −OH groups in unoxidized dextran to iron. In addition, the suboptimal crystallinity of the products partially owing to the low reaction temperature will give rise to low saturation magnetization. In the current work, a green, facile, and general one-pot hydrothermal strategy capable of controlling the average size and size distribution of Fe3O4@O-dextran (oxidized dextran) NPs was successfully developed. The as-synthesized NPs demonstrated controllable size, narrow size distribution, good crystallinity, high saturation magnetization, and especially high T2-weighted MR image signal intensity. Moreover, due to the O-dextran coating, these NPs are pretty stable in many kinds of aqueous media, and the desired biological probes including peptides, DNA, and antibodies can be conjugated onto the Odextran layer via a covalent linkage between the carboxylate group (−COO−) and the amine group (−NH2) in bioprobes. It is noteworthy that, unlike the ordinary coprecipitation method, herein, almost all the iron precursors have been Received: May 29, 2012 Revised: August 27, 2012 Published: September 5, 2012 20558
dx.doi.org/10.1021/jp305211d | J. Phys. Chem. C 2012, 116, 20558−20563
The Journal of Physical Chemistry C
Article
size shown in the TEM image, the Dh value decreased by prolonging the reaction time. This can be attributed to the decrease of the amount of dextran coating on the outerface of the Fe3O4 NPs because the ratio of area-to-volume decreased after the core size increased. As shown in the results of thermogravimetric analysis (TGA) (Figure S5), the weight loss is 28.5%, 23.4%, and 21.6% for NP5, NP10, and NP15, respectively. The sharp mass loss for each sample at relatively low temperature (400 °C) suggests the decomposition of the coating dextran on the particle surface. Thereafter, the weight remains stable until the temperature grows up to c.a. 600 °C. The notable weight increase after 600 °C can be assigned to the transformation of Fe3O4 into Fe2O3 in atmosphere. The magnetic properties of the as-prepared Fe3O4@Odextran nanoparticles were investigated, and the hysteresis loops measured at room temperature (298 K) are shown in Figure 1. The saturation magnetization at 6T is 35.5 (45.3),
transferred into the magnetic nanofluids with controllable size (
