Core–shell Fe3O4@NaLuF4:Yb,Er/Tm nanostructure for MRI, CT and upconversion luminescence tri-modality imaging
Introduction
Recent years have witnessed the rapid pace of research and development of rare earth upconversion nanophosphors (RE-UCNPs) as potential bioimaging agents because of their distinct optical and chemical properties, such as sharp emission lines, long lifetimes, superior photostability and non-photoblinking [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33]. The upconversion luminescence (UCL) process involves the conversion of low-energy light in the near-infrared (NIR) region to higher energy visible light through multiple photon absorption or energy transfer [1], [2], [3], [4], [5], [6], [7], [8]. This special photoluminescence mechanism excludes both conventional luminescent materials (such as QDs and organic dyes) and endogenous fluorescent substances. As a result, RE-UCNPs for photoluminescence bioimaging exhibit many advantages, such as the use of non-invasive NIR radiation and the absence of autofluorescence of biological tissues [11], [12]. In particular, Yb3+ and Tm3+ co-doped RE-UCNPs show intense UCL emission at 800 nm under continuous-wave excitation at 980 nm, and are therefore ideal candidates for high contrast whole-body small-animal imaging [10], [12], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28]. For example, we have recently reported that the detection limit for the UCL imaging of a whole-body mouse is only 50 cells [28].
Usually, photoluminescent imaging has one shortcoming of the low penetration depth of the excitation and emission light, which can be solved by magnetic resonance imaging (MRI) [34], [35] and X-ray computed tomography (CT). To combine the merits of these imaging modalities, multimodal imaging based on RE-UCNPs has been developed. For example, by introducing Gd3+ in the host matrix or on the nanoparticle surface, magnetic-luminescent RE-UCNPs have successfully been fabricated for dual-modal imaging of T1-enhanced MRI and UCL imaging [36], [37], [38], [39]. CT gives high spatial resolution and 3D tomography information about deep anatomic structures due to the high penetration of X-rays, whilst MRI provides comparable resolution but with far better contrast. Considering the different spatial resolution, imaging penetration depth, and areas of application of these different imaging modalities, a combination of CT, MRI and luminescence imaging using a sole probe is urgently required.
Owing to their large magnetic moment, superparamagnetic Fe3O4 nanoparticles have been combined with RE-UCNPs together for fabricating magnetic operation, T2-enhanced MR imaging and UCL imaging [40]. For example, Liu et al. developed multifunctional nanoparticles, NaYF4:Yb,Er@Fe3O4@Au, which combined optical and magnetic properties useful for multimodality imaging [41]. Recently, our group reported an imaging agent with NaYF4:Yb,Tm@FexOy core–shell nanostructure for T2 MRI and UCL bimodal lymphatic imaging [42]. It should be noted that the intensity of UCL emission will be weaker in the presence of the Fe3O4-shielding, because both excitation and emission light are absorbed by the Fe3O4 shell. Therefore, it is expected that a different core–shell nanostructure with Fe3O4 nanoparticles as core and RE-UCNPs as shell might show excellent upconversion luminescent and magnetic properties.
NaLuF4 may be an ideal building block for multimodal bioimaging probes since RE-UCNPs based on the NaLuF4 host have high UCL quantum yield [10], [28]. Furthermore, owing to the large atomic number and high X-ray absorption coefficient of lutetium, NaLuF4 can be used as a contrast agent for CT imaging. In this work, core–shell Fe3O4@NaLuF4:Yb,Er/Tm nanostructure (MUCNP) with Fe3O4 as the core and NaLuF4:Yb,Er/Tm as the shell layer has been designed and synthesized by a step-wise method. The core–shell structure was characterized by transmission electron microscopy (TEM), powder X-ray diffraction (XRD), energy-dispersive X-ray (EDX) analysis and X-ray photoelectron spectroscopy (XPS). The upconversion luminescent, magnetic and X-ray attenuation properties of these nanoparticles were investigated in detail. Moreover, we have also investigated the multimodal performance for MR, CT and UCL imaging following an intratumoral injection of MUCNP. Finally, the cytotoxicity of the MUCNP is described.
Section snippets
Materials
Rare earth oxides Lu2O3 (99.999%), Yb2O3 (99.999%), Er2O3 (99.999%) and Tm2O3 (99.98%) were purchased from Beijing Lansu Co. China. FeCl3·6H2O, trisodium citrate, sodium acetate (NaAc), ethylene glycol, tetraethyl orthosilicate (TEOS), urea, ammonia solution (28 wt%), NaF, HF (40%), absolute ethanol and hydrochloric solution were purchased from Sinopharm Chemical Reagent Co., China. Rare earth chlorides (LnCl3, Ln: Lu, Yb, Er, Tm) were prepared by dissolving the corresponding metal oxide in 10%
Synthesis and characterization of MUCNP
A step-wise method has been developed to synthesize the multifunctional Fe3O4@NaLuF4:Yb,Er/Tm nanostructure (abbreviated as MUCNP). The details of the procedure are summarized in Scheme 1. Firstly, uniform Fe3O4 cores with diameter of ∼180 nm were prepared by a modified polyol method following a procedure described previously [43]. The particles show good dispersibility in polar solvents (such as water and ethanol) due to the capping of citrate groups on the surface. Silica coating was then
Conclusions
A Fe3O4@NaLuF4:Yb,Er/Tm nanophophor (MUCNP) has been developed using a step-wise method. It combines upconversion luminescent, magnetic and X-ray attenuation properties. The T2 magnetic resonance properties result from the Fe3O4 cores, while the NaLuF4:Yb,Er/Tm outer shell shows excellent UCL emission and enhances positive contrast in CT images. The multifunctional MUCNP has been used as an MR, CT and UCL probe for multimodal imaging of mice bearing tumors. In vitro UCL imaging study confirms
Conflict of interest
No financial conflict of interest was reported by the authors of this paper.
Acknowledgments
The authors thank Yonghui Deng, Wei Li, from Department of Chemistry, Fudan University, for thoughful discussions. This work was financially supported by NSFC (20825101), SSTC (1052nm03400 and 11XD1400200), the State Key Basic Research Program of China (2011AA03A407 and 2012CB932403), IRT0911, SLADP (B108) and the CAS/SAFEA International Partnership Program for Creative Research Teams.
References (49)
- et al.
Cubic sub-20 nm NaLuF4-based upconversion nanophosphors for high-contrast bioimaging in different animal species
Biomaterials
(2012) - et al.
Long-term in vivo biodistribution imaging and toxicity of polyacrylic acid-coated upconversion nanophosphors
Biomaterials
(2010) - et al.
Drug delivery with upconversion nanoparticles for multi-functional targeted cancer cell imaging and therapy
Biomaterials
(2011) - et al.
Near-infrared light induced in vivo photodynamic therapy of cancer based on upconversion nanoparticles
Biomaterials
(2011) - et al.
Multifunctional nanoprobes for upconversion fluorescence, MR and CT trimodal imaging
Biomaterials
(2012) - et al.
Tracking transplanted cells in live animal using upconversion fluorescent nanoparticles
Biomaterials
(2009) - et al.
Bioimaging and toxicity assessments of near-infrared upconversion luminescent NaYF4:Yb, Tm nanocrystals
Biomaterials
(2011) - et al.
Targeted dual-contrast T1- and T2-weighted magnetic resonance imaging of tumors using multifunctional gadolinium-labeled superparamagnetic iron oxide nanoparticles
Biomaterials
(2011) - et al.
Dual-modality in vivo imaging using rare-earth nanocrystals with near-infrared to near-infrared (NIR-to-NIR) upconversion luminescence and magnetic resonance properties
Biomaterials
(2010) - et al.
Fluorine-18-labeled Gd3+/Yb3+/Er3+ co-doped NaYF4 nanophosphors for multimodality PET/MR/UCL imaging
Biomaterials
(2011)
Core-shell NaYF4:Yb3+, Tm3+@FexOy nanocrystals for dual-modality T2-enhanced magnetic resonance and NIR-to-NIR upconversion luminescent imaging of small-animal lymphatic node
Biomaterials
Preparation of hollow spherical particles of yttrium compounds
J Colloid Interface Sci
Preparation and properties of uniform coated colloidal particles: V. yttrium basic carbonate on polystyrene latex
J Colloid Interf Sci
Recent advances in the chemistry of lanthanide-doped upconversion nanocrystals
Chem Soc Rev
Small upconverting fluorescent nanoparticles for biomedical applications
Small
Upconversion nanophosphors for small-animal imaging
Chem Soc Rev
Luminescent rare earth nanomaterials for bioprobe applications
Dalton Trans
Rare earth fluoride nano-/microcrystals: synthesis, surface modification and application
J Mater Chem
Simultaneous phase and size control of upconversion nanocrystals through lanthanide doping
Nature
Tuning upconversion through energy migration in core–shell nanoparticles
Nat Mater
Versatile synthesis strategy for carboxylic acid-functionalized upconverting nanophosphors as biological labels
J Am Chem Soc
Facile epoxidation strategy for producing amphiphilic up-converting rare-earth nanophosphors as biological labels
Chem Mater
Laser scanning up-conversion luminescence microscopy for imaging cells labeled with rare-earth nanophosphors
Anal Chem
High contrast upconversion luminescence targeted imaging in vivo using peptide-labeled nanophosphors
Anal Chem
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