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Cite This: ACS Appl. Mater. Interfaces 2018, 10, 12331−12340
Intense Red-Emitting Upconversion Nanophosphors (800 nm-Driven) with a Core/Double-Shell Structure for Dual-Modal Upconversion Luminescence and Magnetic Resonance in Vivo Imaging Applications A-Ra Hong,†,§ Youngsun Kim,‡ Tae Sup Lee,∥ Sehoon Kim,‡ Kwangyeol Lee,§ Gayoung Kim,‡ and Ho Seong Jang*,†,⊥ †
Materials Architecturing Research Center and ‡Center for Theragnosis, Korea Institute of Science and Technology, 5, Hwarang-ro 14-gil, Seongbuk-gu, Seoul 02792, Republic of Korea § Department of Chemistry, Korea University, 145 Anam-ro, Seoul 02841, Republic of Korea ∥ Division of RI Convergence Research, Korea Institute of Radiological & Medical Sciences (KIRAMS), 75, Nowon-ro, Nowon-gu, Seoul 01812, Republic of Korea ⊥ Korea University of Science and Technology, 217, Gajeong-ro, Yuseong-gu, Daejeon 34113, Republic of Korea S Supporting Information *
ABSTRACT: In this study, intense single-band red-emitting upconversion nanophosphors (UCNPs) excited with 800 nm near-infrared (NIR) light are reported. When a NaYF4:Nd,Yb active-shell is formed on the 12.7 nm sized NaGdF4:Yb,Ho,Ce UCNP core, the core/shell (C/S) UCNPs show tunable emission from green to red, depending on the Ce 3+ concentration under excitation with 800 nm NIR light. Ce3+doped C/S UCNPs (30 mol %) exhibit single-band red emission peaking at 644 nm via a 5F5 → 5I8 transition of Ho3+. A high Nd3+ concentration in the shell results in strong absorption at around 800 nm NIR light, even though the shell thickness is not large, and small-sized C/S UCNPs (16.3 nm) emit bright red light under 800 nm excitation. The formation of a thin NaGdF4 shell on the C/S UCNPs further enhances the upconversion (UC) luminescence and sub-20 nm sized core/ double-shell (C/D-S) UCNPs exhibit 2.8 times stronger UC luminescence compared with C/S UCNPs. Owing to the strong UC luminescence intensity and Gd3+ ions on the surface of nanocrystals, they can be applied as a UC luminescence imaging agent and a T1 contrast agent for magnetic resonance (MR) imaging. In vivo UC luminescence and high-contrast MR images are successfully obtained by utilizing the red-emitting C/D-S UCNPs. KEYWORDS: core/shell/shell, upconversion, nanophosphors, in vivo fluorescence imaging, in vivo magnetic resonance imaging
1. INTRODUCTION Lanthanide ion-doped upconversion nanophosphors (UCNPs) are considered as one of the promising fluorescence imaging agents because of their unique optical properties, such as antiStokes shift emission and sharp emission peaks, compared with conventional fluorophores.1,2 The optical features of the UCNPs, such as anti-Stokes shift luminescence, long lifetime, and nonblinking and nonbleaching luminescence, are advantageous for use in bioimaging applications.3−9 In addition, the use of near-infrared (NIR) light as an excitation source for upconversion (UC) luminescence is another advantage in fluorescence imaging utilizing UCNPs since biomolecules do not exhibit autofluorescence under the NIR light illumination, giving rise to a high signal-to-noise ratio.9 Owing to these advantages of UCNPs in biorelated applications, there have been many reports on the synthesis and application of UCNPs over the previous decade.10−22 The UCNPs used in most © 2018 American Chemical Society
previous studies absorb 980 nm NIR light and emit visible light.12,16,17 Unfortunately, the utilization of 980 nm excitation results in the heating of cells and tissues irradiated with the NIR light23,24 because water molecules, which constitute a significant part of the biological system, exhibit a large absorption crosssection in the 980 nm spectral region.25 In addition, as water molecules strongly absorb incident 980 nm light, the penetration depth of the incident light into the tissue becomes short, making the deep tissue imaging difficult. These problems can be solved by using Nd3+- or dye-sensitized UCNPs that exhibit UC luminescence under 800 nm excitation, located in the biologically transparent window.24,26,27 In particular, Nd3+sensitized UCNPs are more favorable than dye-sensitized Received: November 28, 2017 Accepted: March 16, 2018 Published: March 16, 2018 12331
DOI: 10.1021/acsami.7b18078 ACS Appl. Mater. Interfaces 2018, 10, 12331−12340
Research Article
ACS Applied Materials & Interfaces UCNPs owing to the low photostability of organic dyes.28 Yan’s group reported green-emitting NaGdF4:Yb,Er/ NaGdF4:Nd,Yb,24 and Liu’s group reported a NaYF4:Yb,A,Nd (1%)/NaYF4:Nd (20%) (A = Tm, Er, and Ho) core/shell (C/ S) structure,23 in which the activator ions are geometrically separated from the Nd3+ ions to prohibit luminescence quenching of activator ions by energy transfer from the activators to the Nd3+ ions. Since these studies, there have been several reports on the 800 nm NIR light-driven blue/green UC luminescence.29−33 Huang and Lin reported bright green- and blue-emitting UCNPs, with an active-core/active-shell structure under 808 nm excitation.29 Wang et al. applied Nd3+-sensitized NaYF4:Yb,Ho-based UCNPs for fluorescence imaging and photodynamic therapy utilizing 808 nm NIR light.34 Zhong et al. enhanced UC green and blue luminescence from Nd3+sensitized Er/Tm/Ho-activated UCNPs, using a quenching shield sandwich structure.28 Despite these investigations of ∼800 nm NIR light-driven UCNPs, reports on Nd3+-sensitized red-emitting UCNPs are relatively scarce. Recently, Chen et al. reported Nd3+-sensitized single-band red-emitting UCNPs with a C/S structure,35 and Shen et al. reported strong red-emitting UCNPs with an intercalated nanostructure.36 The realization of single-band red light under 800 nm NIR light is believed to be highly advantageous for in vivo bioimaging because both NIR light from an excitation source and red light emitted from the UCNPs lie in the optically transparent window in a biological system.25 However, the particle size for the C/S structure reported previously by Chen et al. was approximately 50 nm,35 which is too large for in vivo application because small UCNPs are desirable for renal clearance.37 Additionally, the intercalate nanostructure makes the synthetic procedure too complicated and gives rise to a larger particle size.36 In a study by Wang et al., in vitro cell imaging was conducted by utilizing a red emission peak from NaYF4:Yb,Ho-based UCNPs, which show UC luminescence peaks at green and red spectral regions; the particle size was also large (45.2 nm), and the green peak showed a higher intensity than the red peak.34 Thus, although 800 nm NIR light-driven red emission is advantageous for in vivo imaging, in vivo imaging utilizing single-band red-emitting UCNPs under ∼800 nm excitation has not yet been reported. In this study, we report on NaGdF 4 :Yb,Ho,Ce/ NaYF4:Nd,Yb/NaGdF4 core/double-shell (C/D-S) structured UCNPs with a very small size (
