Fluorescence-enhanced gadolinium-doped zinc oxide quantum dots for magnetic resonance and fluorescence imaging
Introduction
Magnetic resonance imaging (MRI) is regarded as one of most powerful techniques in modern diagnostic medicine, because it can penetrate deep into tissue, providing anatomical details and high-quality three-dimensional images of soft tissue in a non-invasive monitoring manner [1], [2]. Unfortunately, this technique has just been able to resolve objects larger than a few micrometers in size, thus exhibiting much lower sensitivity than radioactive or optical methods [3], [4], [5]. Fluorescence imaging (FI), in contrast, has much higher sensitivity and the potential for real-time imaging, but with limited depth perception, which restricts their application just to surface or near-surface phenomena [6], [7]. These high complementary characteristics between them allow their respective limitations to be effective overcome by integrating magnetic resonance and optical imaging functionalities into a single nanostructure [8]. As a consequence, intensive efforts have been drawn into the development of MRI-FI nanoprobes due to their prominent advantages in terms of medical diagnose and molecular imaging [9], [10], [11], [12], [13], [14], [15], [16], [17], [18].
Up to now, developing MRI-FI nanoprobes usually adopted two different strategies. One logical strategy was based on incorporating paramagnetic ions into quantum dots (QDs) such as CdSe [9], [10], [11]. These nanoprobes showed good photo-stability, high relaxivity and quantum yield (QY), but their high toxicity and potential pollution hazard as the released Cd+ and Se+ from the surface QDs might limit their biological and medical applications. In addition, selenides or sulfides were intrinsically less-resistant to oxidation by the O2 in air [19], [20]. The other was based on coating a magnetic core and fluorophores with shells such as silica or modifying silica-capped fluorescent cores with paramagnetic ions [12], [13], [14], [15], [16], [17], [18]. Generally, these nanoprobes had lower toxicity compared with those obtained by the above strategy thanks to the encapsulation by silica shell. Meanwhile, they allied high sensitivity of FI to the high spatial resolution of MRI, thus ensuring a better reliability of the collected data. Silica encapsulating involved in the fabrication of these nanoprobes, however, not only made the synthesis more complex and difficult, but also increased the particle’s size [21]. From the viewpoint of practical applications, larger particles were not very suitable for biological and medical fields, especially for labeling functional subcellular or proteins, as larger particles often affect their biological function and are more likely to be recognized and cleared by the phagocyte [22], [23]. For these reasons, it is still a big challenge to develop reasonable strategies for preparing excellent MRI-FI nanoprobes which should be guided by following criteria: 1) high relaxivity and quantum yield, 2) small size, 3) simple and cost-effective synthesis method, 4) low toxicity, and 5) chemical stability in air. Moreover, the nanoprobes will provide better reliability for clinical diagnosis if they are T1-positive agents, since they can enhance the signal intensity instead of reducing the signal intensity in T1-weighted MRI, avoiding the confusion with the reduced signals from bleeding, calcification or metal deposits [24], [25]. Also, we expect that these nanoprobes can give the emission which is more sensitive for human eye instead of blue emission since most cells and tissues also appear blue under UV light [26], [27].
In this study, we presented a simple and versatile method to develop dual modality nanoprobes that satisfied all of these criteria by doping Gd3+ ions in low toxic ZnO QDs. Detail on their synthesis, optical properties, cytotoxicity and applications for in vitro MRI-FI imaging were investigated. Experimental results indicated that these nanoprobes had great potential applications in biological and medical fields.
Section snippets
Materials
Zinc acetate dihydrate was purchased from Beijing Chemical Reagent factory (Beijing, China). Tetramethylammonium hydroxide (TMAH) and Gadolinium acetate hydrate were procured from Alfa Aesar. Oleic acid was obtained from Sigma–Aldrich. Other chemicals were of analytical grade and used without any further purification. Water used throughout all experiments was purified with the Millipore system.
Apparatus
The nanoparticle size was examined using JEOL 2000-FX transmission electron microscopy (TEM). The
Synthesis and characterization
ZnO QDs were produced through hydrolyzing zinc acetate by TMAH in ethanol [28]. Gadolinium doping of ZnO QDs were achieved by replacing partially zinc acetate with gadolinium acetate, and the actual molar ratios of Gd/Zn (designed as x) in the final products was ascertained by inductively coupled plasma mass spectrometry (ICP-MS). Typical transmission electron microscopy (TEM) images in Fig. 1a,b illustrated the diameter of ZnO QDs and Gd-doped ZnO QDs (x = 0.08) was approximately 6 nm and
Conclusions
In summary, we have presented a facile strategy for the fabrication of novel MRI-FI nanoprobes named as Gd-doped ZnO QDs with reduced size. Such nanoprobes exhibited significantly enhanced yellow emission due to the Gd doping. The utility of Gd-doped ZnO QDs as optical imaging agents has been clearly demonstrated. HeLa cells could be successfully imaged in short time and remained high viability even at high dose of QDs, revealing the weak toxicity of Gd-doped ZnO QDs. Furthermore, Gd-doped ZnO
Acknowledgements
Financial support by the “Hundred Talents Project” of Chinese Academy of Sciences, National Basic Research Program of China (973 Program; No.2010CB933600), NSFC (No. 21075117; 20873138), and Alexander von Humboldt Foundation is gratefully acknowledged.
References (39)
- et al.
Biological interactions of quantum dot nanoparticles in skin and in human epidermal keratinocytes
Toxicol Appl Pharmacol
(2008) - et al.
Lipid-based nanoparticles for contrast-enhanced MRI and molecular imaging
NMR Biomed
(2006) Paramagnetic metal complexes as water proton relaxation agents for NMR imaging: theory and design
Chem Rev
(1987)Magnetic resonance imaging: forcing the nanoscale
Nat Nanotechnol
(2009)- et al.
Gadolinium (III) chelates as MRI contrast agents: structure, dynamics, and applications
Chem Rev
(1999) - et al.
Viral nanoparticles donning a paramagnetic coat: conjugation of MRI contrast agents to the MS2 capsid
Nano Lett
(2006) - et al.
High-contrast paramagnetic fluorescent mesoporous silica nanorods as a multifunctional cell-imaging probe
Small
(2008) - et al.
Hybrid gadolinium oxide nanoparticles: multimodal contrast agents for in vivo imaging
J Am Chem Soc
(2007) - et al.
Tat peptide-derivatized magnetic nanoparticles allow in vivo tracking and recovery of progenitor cells
Nat Biotechnol
(2000) - et al.
Synthesis of water-dispersible fluorescent, radio-opaque, and paramagnetic CdS: Mn/ZnS quantum dots: a multifunctional probe for bioimaging
J Am Chem Soc
(2005)
Core/shell quantum dots with high relaxivity and photoluminescence for multimodality imaging
J Am Chem Soc
Synthesis of Gd doped CdSe nanoparticles for potential optical and MR imaging applications
J Mater Chem
Silica-coated nanocomposites of magnetic nanoparticles and quantum dots
J Am Chem Soc
Improved biocompatibility and pharmacokinetics of silica nanoparticles by means of a lipid coating: a multimodality investigation
Nano Lett
Synthesis of silica-coated semiconductor and magnetic quantum dots and their use in the imaging of live cells
Angew Chem Int Ed
Multifunctional uniform nanoparticles composed of a magnetite nanocrystal core and a mesoporous silica shell for magnetic resonance and fluorescence imaging and for drug delivery
Angew Chem Int Ed
Uniform mesoporous dye-doped silica nanoparticles decorated with multiple magnetite nanocrystals for simultaneous enhanced magnetic resonance imaging, fluorescence imaging, and drug delivery
J Am Chem Soc
Synthesis and characterization of fluorescent, radio-opaque, and paramagnetic silica nanoparticles for multimodal bioimaging applications
Adv Mater
Hybrid silica nanoparticles for multimodal imaging
Angew Chem Int Ed
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