Magnetic-NIR Persistent Luminescent Dual-Modal ... - ACS Publications

Subscriber access provided by University of Colorado Boulder

Article

Magnetic-NIR Persistent Luminescent Dual-Modal ZGOCS@MSNs@Gd2O3 Core-Shell Nanoprobes For In Vivo Imaging Rui Zou, Shuming Gong, Junpeng Shi, Ju Jiao, Ka-Leung Wong, Hongwu Zhang, Jing Wang, and Qiang Su Chem. Mater., Just Accepted Manuscript • DOI: 10.1021/acs.chemmater.7b00087 • Publication Date (Web): 10 Apr 2017 Downloaded from http://pubs.acs.org on April 12, 2017

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a free service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are accessible to all readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

Chemistry of Materials is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 12

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 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Chemistry of Materials

Magnetic-NIR Persistent Luminescent Dual-Modal ZGOCS@MSNs@Gd2O3 Core-Shell Nanoprobes For In Vivo Imaging †

†

,†

,†

†

Rui Zou,# Shuming Gong,# Junpeng Shi,‡ Ju Jiao,* Ka-Leung Wong,§ Hongwu Zhang,‡ Jing Wang,* and Qiang Su †

Ministry of Education Key Laboratory of Bioinorganic and Synthetic Chemistry, State Key Laboratory of Optoelectronic Materials and Technologies, School of Chemistry, and Departments of Nuclear medicine, the Third Affiliated Hospital of Sun Yat-sen University, Sun Yat-Sen University, Guangzhou, Guangdong 510275, PR China ‡

Key Lab of Urban Pollutant Conversion, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, Fujian 361021, China §

Department of Chemistry, Hong Kong Baptist University, Hong Kong

# Rui Zou and Shuming Gong contributed equally to this work. ABSTRACT: Recently, Gd3+-based NIR persistent luminescence nanoparticles have been proposed as highly promising multimodal nanoprobes for full-scale visualization medical techniques in early diagnosis of cancer. However, they still face with some problems, such as hampering further functionalization for the loss of available surface, shortening plasma half-life of the probe caused by inevitable size increase and reducing SNR due to significant persistent intensity loss. In this study, a novel core-shell structure Gd3+-based NIR persistent luminescence multimodal probe ZGOCS@MSNs@Gd2O3 for T1-weighted MR imaging and NIR persistent luminescence imaging was successfully synthesized using MSNs as the reaction vessels for ZGOCS nanoparticles and the core for Gd2O3 shell. Compared with previously reported Gd3+-based NIR persistent luminescence based multimodal nanoprobes, the as-prepared nanoparticles enable surface available, no persistent intensity loss and only a slight size increase. Moreover, this multifunctional nanoprobe not only retains excellent NIR persistent luminescence properties with rechargeable ability, but also possesses high longitudinal relaxivity via the Gd2O3 shell, positioning ZGOCS@MSNs@Gd2O3 as highly promising nanoprobe for future multimodal bioimaging.

1. Introduction Visualization techniques including positron emission tomography (PET), computed tomography (CT), magnetic resonance imaging (MRI), optical imaging, ultrasound imaging, and nuclear medicine imaging provide an effective tool in early recognition and diagnosis of malignant diseases, such as cancer.1-8 However, every imaging technique used for cancer diagnosis, has its strengths and limitations as well. A promising alternative technique is the combined usage of optical imaging and MRI. Optical imaging has recently attracted a great deal of attention owing to high imaging sensitivity, low cost of the imaging facilities and suitability for image-guided surgery. Unfortunately, it still suffers from low spatial resolution and limited depth penetration.9, 10 In contrast, MRI provides a visualization method with high spatial resolution, but suffers from limited sensitivity. Therefore, the integration of optical imaging and MRI techniques within one platform is an ideal approach to bridge gaps in sensitivity, spatial resolution, and penetration depth of organisms.11, 12 Recently, a lot of research efforts have been focused on the exploitation of dual-modal imaging probes with magnetic and fluorescence properties.13-16 Among them, Gd3+based fluorescent nanoprobes are one of the best candi-

date for imaging and diagnosis. Owing to seven unpaired 4f electrons, the Gd3+ provides high paramagnetic relaxivity which makes Gd3+-based probes ideal paramagnetic relaxation agents. To date, Gd3+-based fluorescent nanoprobes with various luminous mode, especially Gd3+based quantum dots (QDs) and Gd3+-based upconversion nanoparticles (UCNPs), have been well developed as promising multifunctional imaging nanoprobes.17-19 However, signal attenuation and autofluorescence of intrinsic living tissues caused by excitation or emission of imaging probes, often resulting in poor signal to noise ratio (SNR).20, 21 More recently, a novel optical contrast agent based on near-infrared (NIR) persistent luminescence nanoparticles was reported by Scherman and co-workers.21 Such kind of nanomaterial emits NIR persistent luminescence within the tissue transparency window (650 - 1350 nm) for hours after ceasing of excitation and free from background autofluorescence.22, 23 Compared with conventional optical imaging probes, such as QDs and UCNPs, higher signal to noise ratio can be obtained during the signal acquisition.3, 24, 25 Thus, using NIR persistent luminescence nanoparticles to develop multimodal nanoprobes become a significant work26, 27. So far, some valuable researches

ACS Paragon Plus Environment


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 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

focused on Gd3+-based NIR persistent luminescence nanoparticles were done and major strategies are listed in Figure 1.9, 28 The first strategy to add MRI mode is to conjugate NIR persistent luminescence nanoparticles with gadolinium complexes. Although such kind of combination keeps the excellent NIR persistent luminescence, it also brings a loss of available functional groups on the surface of NPs for targeting perspectives and significant increase in hydrodynamic diameter (~30 nm), that may aggravate reticuloendothelial system (RES) uptake of the probe. To overcome these limitations, second strategy by co-doping Gd3+ into NIR persistent luminescence matrix was proposed. Such co-doping strategy frees the surface of nanoprobes and without any increase of hydrodynamic diameter. However, there is a nonnegligible problem that persistent luminescence intensity of nanoprobes significantly decreases, which is caused by forcing gadolinium in crystallographic-mismatched matrix and could finally lower SNR during imaging. In this work, a novel core-shell structure multimodal imaging probe based on the coverage of Gd2O3 shell (~ 1.5 nm) on the surface of mesoporous silica nanoparticles (MSNs) loaded ZnGa2O4:Cr3+,Sn4+ (ZGOCS@MSNs)for MRI and NIR luminescence imaging was proposed as shown in Figure 1 and successfully prepared. Such a kind of core-shell structure nanoparticles are capable of to be a contrast agent for MRI with high spatial resolution, as well as a long-time in vivo imaging probe with rechargeable ability, that brings high imaging sensitivity associated with NIR persistent luminescence properties. Compared to the first two strategies, as-obtained multimodal imaging probe based on new conception of synthesis strategy not only keeps the excellent NIR persistent luminescence but also holds targeting perspectives by freeing the surface of probes. Moreover, only a slight increase (~ 1.5 nm) can be observed in diameter. To the best of our knowledge, no such core-shell approach have been reported to prepare Gd3+-based NIR persistent luminescence multimodal probes for in vivo multimodal imaging so far. 2.

Experimental section

Synthesis of MSNs: The MSNs were prepared according to a previous literature with some modification.29 In a typical procedure, 280 ml water, 80 ml ethanol, 5.728 g CTAB and 0.5 ml ammonium hydroxide were mixed together and stirred for 30 min. After further stirring in an oil bath at 60 °C for 30 min, 14.6 ml TEOS was dropped into the mixture within 2 min. The reaction was kept at 60 °C for2 h before being cooled down to room temperature. Then the samples were collected by centrifugation, washed with ethanol and water three times and dried at 60 °C for 12 hours. Finally, MSNs was obtained after annealing at 550 °C for 5 h to remove CTAB templates. Synthesis of ZGOCS@MSNs: The ZGOCS@MSNs were synthesized by a MSNs template method with some modifications. Typically, 2 ml Ga(NO3)3 solution (1 M), 0.2195 g Zn(CH3COO)2·2H2O, 0.0036 g Cr(CH3COO)3 and 0.0056

Page 2 of 12

g SnCl4 were mixed to form a precursor solution. The atom molar ratio of Ga/Zn/Cr/Sn was fixed to be 1.98/1/0.01/0.01. Then, 0.4 ml precursor solution was intensively mixed with 0.2 g MSNs and the mixture was dried in a vacuum oven at 60 °C for 12 hours. The dried sample was pre-sintered at 600 °C for 2 h with a heating rate of 5 °C/min. After being ground into a fine power, the pre-sintered material was annealed at 1000 °C for 4 h with a slow heating rate of 2 °C/min. Finally, the ZGOCS@MSNs were obtained after cooling down to room temperature. Synthesis of ZGOCS@MSNs@Gd2O3: Typically, 0.2 ml Gd(NO3)3 solution (0.1 M) and 0.1201 g urea were added in 50 ml water in a 100 ml flat bottom flasks and the solution was thoroughly stirred for 30 min. Subsequently, 0.2 g of as-obtained ZGOCS@MSNs were added and well dispersed into the above solution by sonication for 2 h. The mixture was heated at 98 °C and at same time was vigorously stirred for 1 h before being cooled down to room temperature. Then, the as-prepared nanospheres were collected by centrifugation and washed with deionized water and ethanol several times. The final product ZGOCS@MSNs@Gd2O3nanospheres were obtained after annealing at 750 °C for 2 h in air in a muffle furnace with a slow heating rate of 2 °C/min. The thickness of the asobtainedGd2O3 shell coated outside is about 1.5 nm. 0.5 ml and 1 ml of Gd(NO3)3 were used to obtain about 4.2 nm and 6.1 nm Gd2O3 shell coated on the surface of ZGOCS@MSNs nanospheres. Surface functionalization of ZGOCS@MSNs@Gd2O3. 20 mg ZGOCS@MSNs@Gd2O3 were added into 10 mL 5mmol/L NaOH solution under overnight vigorous magnetic stirring at room temperature. The as-obtained ZGOCS@MSNs@Gd2O3-OH nanospheres were collected by centrifugation, and washed with deionized water three times. 10 mg ZGOCS@MSNs@Gd2O3-OH nanospheres were dispersed in 4 mL dimethylformamide (DMF) with the assistance of sonication. Then 40 ul 3-aminopropyltriethoxysilane (APTES) was added under vigorous stirring for 5 hours at room temperature. The as-obtained ZGOCS@MSNs@Gd2O3-NH2 nanoparticles were collected by centrifugation. Unreacted APTES was removed by washing with DMF three times. 5 mg ZGOCS@MSNs@Gd2O3-NH2nanospheres were initially dispersed in 2 ml PBS (pH=7.4) by sonication, and then 50 mg SC-PEG-COOH (average MW=3400) was added. To ensure the reaction completeness, the mixture was gently stirred for 24 h in the dark at room temperature. Finally, the as-obtained ZGOCS@MSNs@Gd2O3-PEG nanospheres were collected by centrifugation and washed three times with PBS to remove unreacted PEG. Characterization. XRD patterns were recorded by using powder x-ray diffraction (XRD, Rigaku D/MAX 2200 VPC) at a scanning rate of 10 °/min in the 2θ range from 10° to


2

Page 3 of 12

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 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


70°, with Cu Kα1 radiation (λ=1.5405 Å). The morphologyand structure of the as-prepared products were inspected using scanning electron microscopy (SEM, FEI Quanta 400).Transmission electron microscopy (TEM) micrograph, high-resolution TEM (HRTEM) micrograph and high-angle annular dark field scanning (HAADFSTEM) images were obtained from FEI Tecnai G2 F30. The persistent luminescence signals were obtained using HORIBA JY FL3-21. Photoluminescence excitation (PLE) and emission (PL) spectra were determined on a FSP920combined Time Resolved and Steady State Fluorescence Spectrometer (Edinburgh Instruments) with a 450 W xenon lamp as the excitation source. The hydrodynamic size and zeta potential were measured on Nanoparticle size-Zeta potential and molecular weight analyzer (Brookhaven). N2 adsorption/desorption isotherms were obtained by using a gas adsorption analyzer (ASAP 2020M), the specific surface area was calculated by the Brunauer–Emmett–Teller (BET) method. Cytotoxicity Assay. In vitro cytotoxicity of the ZGOCS@MSNs@Gd2O3-PEG was assessed using a MTT assay. L02 and MCF-7 cells were seeded into 96-well plates and grown for 12 h in a CO2 incubator (Hera cell, Germany). Then, the old medium was removed, and fresh medium containing various concentrations of ZGOCS@MSNs@Gd2O3-PEG was added into cells and incubated for another 24 h in a CO2 incubator. To measure the toxicity, MTT (0.5 mg/mL) was added to each well for 4 h at 37 oC. Subsequently, DMSO was added to each well, and the plate was shaken for 20 min on a plate shaker. The absorbance was then measured at 490 nm using a microplate reader (Molecular Devices, USA) In vitro and in vivo MRI: In vitro T1-weighted and T2weighted MR images and relaxation time measurements were performed using a 1.5-T clinical MRI instrument (Achieva; Philips Medical Systems, Best, the Netherlands) with an 11-cm circular coil. ZGOCS@MSNs@Gd2O3nanospheres were dispersed in 1% agarose gel with various Gd3+ concentrations (0, 0.037, 0.09, 0.111, 0.148, 0.18 mM). Fast spin echo (FSE) T1weighted and T2-weighted images were acquired using the following parameters: TR/TE=500/15ms, NSA=2, FOV= 100 mm × 100 mm, matrix=256×256 and section thickness= 2 mm; TR/TE=2600/100 ms, NSA=4, FOV= 100 mm × 100 mm, matrix=256×256 and section thickness= 2 mm. T1 and T2 relaxation data were acquired by using single-section multi-spin-echo sequences with the following parameters: TR=4000，3500 ms, TE=20 ms, stepped echo time=20–160 ms for eight steps; echo spacing=20 ms; TR=2000 ms, TE=20 ms, stepped echo time=20–160 ms for eight steps; echo spacing=20 ms. The r1 and r2 relaxivity values were obtained through the curve fitting of relaxation time 1/T1 (s−1) or 1/T2 (s−1) vs. the concentration of Gd3+ (mM), and the slope of fitting line provides the r1 and r2 relaxivity values.

erlands) with a small animal coil. Typically, the ZGOCS@MSNs@Gd2O3 nanoparticles in phosphate buffer solution (PBS, pH 7.4) was injected into the anesthetized Kunming mouse by tail intravenous injection. Imaging was performed by a fast spin echo imaging sequence (TR/TE = 594.3/12 ms, FOV = 4 cm × 3 cm, matrix=256 × 256，In-plane resolution= 156 μm × 117 μm and slice thickness = 1.0 mm) at two time intervals (pre-injection, 10 min). All studies involving animals were approved by the university animal care and use committee. In vivo NIR persistent luminescence imaging. The ZGOCS@MSNs@Gd2O3-PEG solution (100 μL, 2 mg mL-1) was injected through the tail vein into a normal mouse after 5 min irradiation of 254 nm UV light. The NIR persistent luminescence signals were subsequently acquired on an IVIS Lumina II imaging system. In vivo recharging imaging was performed right after 120 s of in situ excitation by a white LED flashlight (2650 lumen, NITECORE TM15) used as the light source. The exposure time was set as 60 s in all of the imaging experiments. All studies involving animals were approved by the university animal care and use committee. 3.

Results and Discussion

The design and fabrication procedures of core-shell structural ZGOCS@MSNs@Gd2O3 were illustrated in Scheme 1. Firstly, the MSNs were prepared by a traditional method with some modifications which is described in detail in experimental.29 Then, the nanopores of the as-obtained MSNs were employed as reaction vessels to produce ZGOCS nanoparticles by ionic impregnation and postannealing. Furthermore, Gd2O3 shells were coated on the surface of ZGOCS@MSNs to obtain the multimodal probeZGOCS@MSNs@Gd2O3. In order to increase its colloidal stability and slow down the RES uptake, a classical three-step procedure of surface modification was performed. Initially, ZGOCS@MSNs@Gd2O3 nanoparticles were treated with NaOH to introduce hydroxyl groups (OH) and form ZGOCS@MSNs@Gd2O3-OH. Subsequently, APTES was adopted to transfer -OH into the amino (NH2) functional group on the surface of ZGOCS@MSNs@Gd2O3. Finally, the surface of ZGOCS@MSNs@Gd2O3 was further functionalized with polyethylene glycol (PEG) for improving water dispersion and biocompability.30

The in vivo MR imaging was conducted on clinical 1.5-T system (Achieva; Philips Medical Systems, Best, the Neth-


3


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 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 4 of 12

Figure 1. A comparison of characteristics for three major strategies of preparation of multimodal imaging nanoprobe. Here, an effective multifunctional bioimaging probe ZGOCS@MSNs@Gd2O3-PEG with MRI capability and bright NIR persistent luminescence was obtained. Figure 2 shows the XRD patterns of the as-prepared MSNs, the as-synthesized ZGOCS@MSNs precursor nanospheres and final product ZGOCS@MSNs@Gd2O3. It is clearly seen

Scheme 1. Schematic illustration for the preparation and surface functionalization of core-shell structural ZGOCS@MSNs@Gd2O3. in Figure 2b that all the characteristic XRD peaks of asobtained ZGOCS@MSNs nanospheres match quite well with literature values (JCPDS NO. 38-1240) and can be therefore ascribed to the pure cubic phase ZnGa2O4. A broad diffraction peak can be observed between 15° and 30°, due to the characteristic signals from amorphous MSNs, which is consistent to XRD pattern of as-prepared MSNs as shown in Figure 2a. The final product ZGOCS@MSNs@Gd2O3 gives several new weak peaks at 2θ = 28°, 48° and 56°, which can be indexed as (222), (440) and (622) planes of Gd2O3 (JCPDS NO. 11-0608), respectively, indicating the existence of Gd2O3 (Figure 2c).

Figure 2. XRD patterns of as-synthesized ZGOCS@MSNs@Gd2O3, ZGOCS@MSNs, MSNs and JCPDS standard patterns of Gd2O3 and ZnGa2O4. The typical SEM and TEM images are presented in Figure 3. The SEM image and the corresponding size distributions of MSNs (Figure 3a and Figure S1) show that asprepared MSNs are uniform, mono-disperse, and spherical nanoparticles with a mean diameter of 91.5 nm. The mesoporous structure can be clearly observed from TEM image of MSNs (Figure 3b) and strongly supported by the corresponding N2 adsorption/desorption isotherm and pore-size distribution of MSNs (Figure S2). The Brunauer–Emmet–Teller (BET) surface area and Brunauer– Joyner–Halenda (BJH) average pore size were estimated to be 679.7117 m2 g-1 and 2.5 nm (Figure S2, inset), respectively. The SEM image (Figure 3c) shows that as-obtained ZGOCS@MSNs nanoparticles still are uniform, monodisperse and spherical, indicating that the MSNs can survive during the calcination at 1000 oC. From the TEM image shown in Figure 3d, it is easy to be found that ZGOCS nanoparticles (dark spots on the photomicrograph ) distribute in the nanopores of the MSNs. Comparatively, The SEM and TEM images of ZGOCS@MSNs@Gd2O3 show no apparent morphological change (Figure 3e) but obvious dark circles on the photomicrograph (Figure 3f). Satisfyingly, Gd2O3 shells are successfully coated on the surface of ZGOCS@MSNs and only a slight increase in diameter, which is the key factor of impacting RES uptake of bioprobe, can be observed.


4

Page 5 of 12

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 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Figure 4. (a) HRTEM image and (b) SAED pattern of ZGOCS@MSNs@Gd2O3, (c) High angle annular dark field scanning transmission electron microscopy (HAADFSTEM) images and (d-g) HAADF-STEM-EDS mapping images of ZGOCS@MSNs@Gd2O3 performed in (c) Figure 3. SEM and TEM images of (a, b) MSNs, (c, d) ZGOCS@MSNs and (e, f) ZGOCS@MSNs@Gd2O3. HRTEM image (Figure 4a) taken at the edge from a selected ZGOCS@MSNs@Gd2O3 nanosphere shows that Gd2O3 shell is about 1.5 nm and the interplanar spacing of 0.29 nm corresponds to the (220) plane of cubic phase ZnGa2O4. Furthermore, the SAED pattern (Figure 4b) of a typical selected area of ZGOCS@MSNs@Gd2O3 exhibits a multicrystalline feature and can be indexed to the (220), (311), (400), (511) and (440) planes of the cubic spinel ZnGa2O4structure. To further confirm the formation of core-shell structure of ZGOCS@MSNs@Gd2O3 nanospheres, the elemental analysis was performed. It is clearly shown in the HAADF-STEM image (Figure 4c) and STEM-EDS elemental mapping (Figure 4d-4g) that the elemental distribution of Ga and Zn are in the nanopores and that of Gd is in the shell. As Si is the main component of MSNs template, it is no doubt that Si distributes over the whole nanospheres. All these results indicate that ZGOCS@MSNs@Gd2O3 core-shell structure was successfully synthesised.

The persistent luminescence intensity and afterglow time of ZGOCS@MSNs nanoparticles were optimized by codoping Cr3+/Sn4+. As shown in Figure 5a, the persistent luminescence intensity initially increases and then decreases with the increasing content of Cr3+ ion. The most intense persistent luminescence was obtained at 1 mol %Cr3+. Moreover, it was reported that the Sn4+/Cr3+ codoped ZnGa2O4 gave more intense persistent luminescence than the single Cr3+-doped ZnGa2O4, due to its important role in increasing the amount of antisite defects which is the responsible for persistent luminescence of Cr3+ in ZnGa2O4 host.31, 32 It is indeed seen in Figure 5a that, introducing Sn4+ ions into ZnGa2O4 host is beneficial to persistent luminescence of Cr3+ and the optimal concentration of Sn4+ ion is estimated to be 0.2 mol %. Furthermore, we also investigate the effect of Gd2O3 coating on the persistent luminescence intensity and afterglow time of the ZGOCS@MSNs (Figure 5b). As shown in Figure S3, the thickness of Gd2O3 shell varied with the amount of Gd(NO3)3 used in the synthesis. Satisfactory, there is no obvious decrease of persistent luminescence intensity and afterglow time after coating Gd2O3 shell on the surface of ZGOCS@MSNs nanospheres, as shown in Figure 5b. Contrarily, a slight enhancement of persistent luminescence intensity of ZGOCS@MSNs can be observed when the thickness of Gd2O3 shell is about 1.5 nm (Figure S3). Such a slight enhancement may be ascribed to the surface passivation effect caused by Gd2O3 shell.33


5


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 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 6 of 12

Figure 5. The NIR persistent luminescence decay curves of ZGOCS@MSNs@Gd2O3 nanoparticles monitored at 695 nm after 254 nm UV light illumination for 5 min: (a) ZGOCS@MSNs with various contents of Cr3+/Sn4+ (b) ZGOCS@MSNs@Gd2O3 with various amounts of Gd(NO3)3. The PL excitation and emission spectra of ZGOCS@MSNs@Gd2O3 power at room temperature were recorded as shown in Figure 6a. Under 265 nm, the ZGOCS@MSNs@Gd2O3 powder gives several narrowband emissions ranging from 600 to 800 nm, due to the spin-forbidden 2E →4A2 transition and its phonon sidebands of Cr3+ in the octahedral site of a spinel structure. Similar to the work reported previously, the zero phonon R line, which is originated from CrR (Cr3+ in undistorted octahedral sites), were observed at 688 nm.31, 34 The Stokes (S) and anti-Stokes (AS) phonon side bands of R line locate at right and left side of R line, respectively. Whereas N2 line, which is originated from CrN2 (Cr3+ in distorted octahedral sites, an antisite defect as first cationic neighbor), was observed at 695 nm. The PL excitation spectrum of ZGOCS@MSNs@Gd2O3, monitored at 695 nm emission, exhibits four characteristic broad excitation bands peaking at 265, 310, 420 and 560 nm, respectively. The excitation band at 265 nm is ascribed to the charge transfer band of O2--Ga3+ in ZnGa2O4 host, and those at 310, 420 and 560 nm

Figure 6. (a) Excitation (dotted curve, emission at 695 nm) and emission (solid curve, excitation at 265 nm) spectra of ZGOCS@MSNs@Gd2O3 nanospheres at room temperature. The inset shows the digital photos of ZGOCS@MSNs@Gd2O3 nanospheres powder under irradiation of 254 nm UV light. (b) The NIR persistent luminescence decay curve of ZGOCS@MSNs@Gd2O3 nanospheres monitored at 695 nm by using a xenon lamp as the light source. The inset is the NIR persistent luminescence emission spectrum recorded at 5 s after 5 min irradiation of 254 nm UV light. (c) Excitation (dash curve, emission at 695 nm) and emission (solid curve, excitation at 265 nm) spectra of ZGOCS@MSNs@Gd2O3 aqueous solution at room temperature. The inset shows the digital photos of ZGOCS@MSNs@Gd2O3 aqueous solution under irradiation of 254 nm UV light.


6

Page 7 of 12

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 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


are attributed to the 4A2→4T1(4P), 4A2→4T1(4F) and 4A2→ 4 T2(4F) transitions of Cr3+, respectively. Since the overlapping with charge transfer band of ZnGa2O4 host (265 nm), it is difficult to clearly identify 4A2→4T1(4P) band of Cr3+ (310 nm). The NIR persistent luminescence decay curve of ZGOCS@MSNs@Gd2O3 nanospheres was monitored at 695 nm after 265 nm UV light illumination (xenon lamp as the light source) for 5 min at room temperature as shown in Figure 6b. The result demonstrates that the NIR persistent luminescence of ZGOCS@MSNs@Gd2O3 nanospheres can last longer than 7200 s and still hold appreciable intensity. Moreover, the NIR persistent luminescence emission spectrum of ZGOCS@MSNs@Gd2O3nanospheres was recorded as shown in the inset of Figure 6b. It is noteworthy that the N2 line of Cr3+ is highly predominant in NIR persistent luminescence emission curve. That is to say, the persistent luminescence of ZnGa2O4:Cr3+ is mainly originated from CrN2 ions, which is strongly verified in previous literature.31, 35 We also investigate the PL excitation and emission spectra of the aqueous dispersion of ZGOCS@MSNs@Gd2O3 (Figure 6c). Compared to the ZGOCS@MSNs@Gd2O3 powder, the aqueous dispersion of ZGOCS@MSNs@Gd2O3 exhibits almost the same profile of the PL excitation and emission curves except the relatively weak excitation intensity at 420 nm and 560 nm. The intensity decrease of these two excitation bands is probably due to the quenching effect of the O−H vibration of water.36

the ZGOCS@MSNs@Gd2O3-PEG even with the concentration as high as 200 mg/L. The results indicate the low toxicity of the ZGOCS@MSNs@Gd2O3-PEG.

Figure 8. (a) In vivo T1-weighted MR images of the mouse before and after intravenous injection of ZGOCS@MSNs@Gd2O3 (0.4 mg). (b) Colored graphs correspond to their counterparts in (a). (c) Comparison of the SNR from in vivo T1-weighted images in mouse liver before and after the intravenous injection of ZGOCS@MSNs@Gd2O3 PBS. Figure 7. (a) T1 and T2-weighted in vitro MR images of ZGOCS@MSNs@Gd2O3 and Gd-DTPA with various concentrations. (b) T1 and (c) T2-relaxation rate as a function of Gd3+ concentration of ZGOCS@MSNs@Gd2O3 and GdDTPA. It is essential to evaluate the cytotoxicity of nanoprobes for their potential biological applications. The cytotoxicity of the ZGOCS@MSNs@Gd2O3-PEG was tested on L02 normal liver cells and MCF-7 human breast cancer cells by MTT assay (Figure S4). No significant toxicity to these two different cells was observed after 24 h treatment of ZGOCS@MSNs@Gd2O3-PEG and the viability of two different cells is still higher than 80% after incubation with

Hereafter the multimodal probe capabilities of ZGOCS@MSNs@Gd2O3 nanospheres for MRI (Figure 7 and 8) and optical (Figure 9 and 10) application will be demonstrated and discussed. Figure 7a shows T1 and T2weighted MR images of the ZGOCS@MSNs@Gd2O3 and commercial Gd-DTPA with various concentrations of Gd3+. For T1-weighted MR images, the MR signals from ZGOCS@MSNs@Gd2O3 and Gd-DTPA are both obviously positively enhanced as the concentration of Gd3+ increases from 0 to 0.74 mM. But for T2-weighted MR images, the negatively enhanced effect of ZGOCS@MSNs@Gd2O3 is much better than that of Gd-DTPA. Through the slope of the dependence of relaxation rate 1/T1 or 1/T2 on Gd3+ concentration (Figure 7b and c), the longitudinal (r1) and


7


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 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

transversal relaxivity (r2) of ZGOCS@MSNs@Gd2O3 are determined to be 9.16 mM−1s−1 and 35.51 mM−1s−1 on the 1.5 T MRI system, which are higher than that of commercial T1 type contrast agent Gd-DTPA (r1=6.13, r2=5.68). Moreover, the r2/r1 ratio of ZGOCS@MSNs@Gd2O3 is found to be 3.88, which is 4 times higher than that of Gd-DTPA (r2/r1=0.93). The experimental results indicate that ZGOCS@MSNs@Gd2O3 can be employed as an effective MRI contrast agent. We further performed the in vivo T1-weighted MR images of Kunming mouse before and after intravenous injection of ZGOCS@MSNs@Gd2O3 PBS (200 μL, 2 mg·mL−1) on a 1.5 T clinical MR imaging system (GE SignaExcirte) with a small animal coil. In vivo T1-weighted MR images and corresponding colored graphs are presented in Figure 8a and b. The T1-weighted MRI signal is significantly enhanced in the liver site of the mouse with high spatial resolution (Figure 8a). The corresponding colored graphs provide a clearer representation of distribution of MR signal in the site of liver. Moreover, the SNR from T1-weighted images in mouse liver before and after the intravenous injection of ZGOCS@MSNs@Gd2O3 PBS were compared and shown in Figure 8c. Compared to the reference mouse, the SNR from T1-weighted images in mouse liver after the intravenous injection of ZGOCS@MSNs@Gd2O3 PBS was increased by 46.2%. The above results show that the asobtained ZGOCS@MSNs@Gd2O3 nanospheres possess remarkable MR contrast effect, indicating that the ZGOCS@MSNs@Gd2O3 nanospheres could be used as an effective contrast agent for T1 -weighted MR imaging.

Figure 9. (a) Zeta potential of ZGOCS@MSNs@Gd2O3, ZGOCS@MSNs@Gd2O3-NH2 and ZGOCS@MSNs@Gd2O3PEG in deionized water. (b) The mean hydrodynamic diameter of ZGOCS@MSNs@Gd2O3 and ZGOCS@MSNs@Gd2O3-PEG in deionized water. (c) Visible preview and (d) in vivo imaging of a mouse at 1 min after intravenously injected with ZGOCS@MSNs@Gd2O3-

Page 8 of 12

PEG aqueous solution (2 mg/ml, 5 min excitation with 254 nm UV light before injection). Beside MRI, we will show the optical probe capability of ZGOCS@MSNs@Gd2O3nanospheres as follow. Benefited from available surface, surface functionalization was easily performed on ZGOCS@MSNs@Gd2O3 nanospheres to improve the water dispersion and slow down RES uptake.37, 38 Figure 9a and 9b show the data of zeta potential and hydrodynamic diameter, both of which were employed to assess surface functionalization. Initially, the bare ZGOCS@MSNs@Gd2O3nanospheres exhibit negative surface zeta potential (-16.39 mV) in aqueous solution. After reacting with APTES, they have positive zeta potential (10.92 mV), which proves that NH2 was successfully modified on the surface of ZGOCS@SiO2@Gd2O3. Finally, the zeta potential of ZGOCS@SiO2@Gd2O3-PEG shifts to 12.95 mV after PEGylation (Figure 9a). Meanwhile, the mean hydrodynamic diameter increases from 60.88 nm for bare ZGOCS@SiO2@Gd2O3 to 100.47 nm for ZGOCS@SiO2@Gd2O3-PEG (Figure 9b). All these results above prove the existence of PEG chain on the surface of ZGOCS@SiO2@Gd2O3.

Figure 10. In vivo recharging NIR persistent luminescence images of a normal mouse after intravenous injection of ZGOCS@MSNs@Gd2O3-PEG (0.2 mg). (a-e) First charging, (f-j, k-o, p-t) Repeated imaging after second, third, and fourth in situ excitations with a white LED flashlight (2650 lm) light source for 120 s at time intervals of 10 min. To estimate bio-imaging capability of these PEGylated ZGOCS@SiO2@Gd2O3 for use as the optical probe, an imaging experiment was performed on a living mouse. After


8

Page 9 of 12

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 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


254 nm UV light excitation for 5 min, the pre-excited ZGOCS@SiO2@Gd2O3-PEG aqueous solution (100 μL, 2 mg/mL) was injected into a normal mouse through the tail vein. As shown in Figure 9d, the NIR persistent luminescence signals could be detected in the whole mouse body without any excitation source. Because of the RES uptake, the in vivo imaging signals are mainly enriched in the liver and spleen tissues. An outstanding SNR of 28.55 is obtained in the liver area of mouse at the beginning (Figure S5 and Figure 9d).

ZGOCS@MSNs@Gd2O3, the detection of NIR persistent luminescence probes are no longer limited by the decay behavior of traditional persistent luminescence. In summary, all these results demonstrate that ZGOCS@SiO2@Gd2O3 are capable of long-time in vivo imaging via repeated in situ excitation by white LED light. The relative long-term biodistribution of the ZGOCS@MSNs@Gd2O3-PEG in normal mice was studied by ex vivo NIR luminescence imaging of harvested organs collected from the same mice at 24 h after intravenous injection of ZGOCS@MSNs@Gd2O3-PEG (0.2 mg) (Figure 11a).The region-of-interest function analysis on the ex vivo luminescence images was used to semiquantitatively assess the biodistribution of the ZGOCS@MSNs@Gd2O3PEG in representative organs. (Figure 11b). Combined with qualitative and semiquantitative results in Figure 11a and b, it can be found that the NIR luminescence signal can be detected in various organs, including the lung, liver, spleen, stomach and intestine. It was worth noting that lung and liver had much stronger NIR luminescence signal than other organs. Such finding would be of interest if these two organs were the targeted ones. Moreover, strong signals also could be detected in the intestine and faeces, which suggested that ZGOCS@MSNs@Gd2O3-PEG nanoprobes were able to be excreted through faeces. The widespread organ distribution and long-term circulation suggest the potential of the ZGOCS@MSNs@Gd2O3-PEG nanoprobes for the targeting of cancer or cardiovascular diseases. 4.

Figure 11. (a) Ex vivo NIR luminescence images of heart, lung, liver, spleen, kidney, stomach, intestine and urine from a normal mouse at 24 h after intravenous injection of ZGOCS@MSNs@Gd2O3-PEG (0.2 mg). (b) Corresponding biodistribution for each isolated organ of mouse. To evaluate the in vivo chargeable ability of ZGOCS@MSNs@Gd2O3-PEG, repeated in vivo recharging NIR persistent luminescence images of a normal mouse after intravenous injection of ZGOCS@MSNs@Gd2O3PEG were collected in Figure 10. After irradiation with a white LED flashlight (2650 lm) source for 120 s, it is satisfactorily seen that NIR persistent luminescence signal could be repeatedly observed all over the whole mouse body and last for a long time after first, second, third, and fourth in situ excitations. Interestingly, no significant difference in NIR persistent luminescence signal can be observed between these four in situ excitations. Benefiting from this fantastic chargeable property of

Conclusions

In summary, Gd3+-based NIR persistent luminescence multimodal probe ZGOCS@MSNs@Gd2O3 for T1-weighted MRI and NIR persistent luminescence imaging was successfully synthesized using MSNs as the reaction vessels. Owing to the new conception of synthesis strategy we adopted, as-synthesized ZGOCS@MSNs@Gd2O3 have advantages on surface available, without persistent intensity loss and only a slight increase in hydrodynamic diameter. This multifunctional nanosphere not only preserves excellent NIR persistent luminescence properties with rechargeable ability, but also possesses high longitudinal relaxivity via the Gd2O3 shell. We expect this study to provide an alternative strategy for the design and fabrication of novel NIR persistent luminescence nanoparticles based multifunction nanoprobes.

ASSOCIATED CONTENT Supporting Information. N2 adsorption/desorption isotherm, Size distribution, TEM photographs, cytotoxicity data, calculation of SNR, additional figures and tables as noted in the text. This material is available free of charge via the Internet at http: //pubs.acs.org.

AUTHOR INFORMATION Corresponding Author


9


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 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

*E-mail: [email protected]. 84112112.Fax: +86-20-84111038.

Phone:

+86-20-

Page 10 of 12

tomography and biomagnetic imaging. Biomaterials. 2012, 33, (36), 9232-9238.

Author Contributions All authors have given approval to the final version of the manuscript.

(7). Kang, B. K.; Lim, H. D.; Mang, S. R.; Song, K. M.; Jung,

Notes The authors declare no competing financial interest.

(OH) 2 by a hydrothermal method. CrystEngComm 2015, 17,

M. K.; Yoon, D. H., Synthesis and characteristics of ZnGa 2 O 4 hollow nanostructures via carbon@ Ga (OH) CO 3@ Zn

(11), 2267-2272.

ACKNOWLEDGMENT

(8). Li, Z.; Zhang, Y.; Wu, X.; Huang, L.; Li, D.; Fan, W.; Han,

This work was financially supported by the NSFC (51572302 and 21271191), the “973” programs (2014CB643801), the Joint Funds of the National Natural Science Foundation of China and Guangdong Province (U1301242), Teamwork Projects of Guangdong Natural Science Foundation (S2013030012842), Guangdong Science & Technology Project (2013B090800019 and 2015B090926011) and Natural Science Foundation of Guangdong Province (2014A030313114 and 2016A030313241).

G., Direct aqueous-phase synthesis of sub-10 nm “luminous

REFERENCES

Nanophosphors as Versatile Tool for Multimodal In Vivo

(1). Liu, Q.; Sun, Y.; Li, C.; Zhou, J.; Li, C.; Yang, T.; Zhang,

Imaging. Adv. Funct. Mater. 2015, 25, (2), 331-338.

X.; Yi, T.; Wu, D.; Li, F., 18F-labeled magnetic-upconversion

(10). Townsend, D., Multimodality imaging of structure and

nanophosphors

function. Phys. Med. Biol. 2008, 53, (4), R1-R39.

via

rare-earth

cation-assisted

ligand

pearls” with enhanced in vivo renewable near-infrared persistent luminescence. J. Am. Chem. Soc. 2015, 137, (16), 5304-5307. (9). Maldiney, T.; Doan, B. T.; Alloyeau, D.; Bessodes, M.; Scherman, D.; Richard, C., Gadolinium-Doped Persistent

assembly. Acs Nano 2011, 5, (4), 3146-3157.

(11). Xia, A.; Chen, M.; Gao, Y.; Wu, D.; Feng, W.; Li, F., Gd

(2). Wong, H.-T.; Tsang, M.-K.; Chan, C.-F.; Wong, K.-L.;

3+

Fei, B.; Hao, J., In vitro cell imaging using multifunctional

nanophosphors for trimodality imaging of NIR-to-NIR

small sized KGdF 4: Yb 3+, Er 3+ upconverting nanoparticles

upconversion luminescence, X-Ray computed tomography

synthesized by a one-pot solvothermal process. Nanoscale

and magnetic resonance. Biomaterials. 2012, 33, (21), 5394-

2013, 5, (8), 3465-3473.

5405.

(3). Maldiney, T.; Bessière, A.; Seguin, J.; Teston, E.; Sharma,

(12). Yang, D.; Dai, Y.; Liu, J.; Zhou, Y.; Chen, Y.; Li, C.; Lin,

S. K.; Viana, B.; Bos, A. J.; Dorenbos, P.; Bessodes, M.;

J., Ultra-small BaGdF 5-based upconversion nanoparticles as

Gourier, D.; Scherman, D.; Richard, C., The in vivo activation

drug carriers and multimodal imaging probes. Biomaterials.

of

2014, 35, (6), 2011-2023.

persistent

nanophosphors

for

optical

imaging

of

complex-modified

NaLuF

4-based

upconversion

vascularization, tumours and grafted cells. Nat. Mater. 2014,

(13). Li, A.-H.; Lü, M.; Yang, J.; Chen, L.; Cui, X.; Sun, Z.,

13, (4), 418-426.

Upconversion-luminescent/magnetic dual-functional sub-20

(4). Lin, J.; Wang, M.; Hu, H.; Yang, X.; Wen, B.; Wang, Z.;

nm

Jacobson, O.; Song, J.; Zhang, G.; Niu, G., Multimodal-

heteronanoparticles. Dalton Trans. 2016, 45, (13), 5800-5807.

Imaging-Guided

Versatile

(14). Park, Y. I.; Kim, H. M.; Kim, J. H.; Moon, K. C.; Yoo, B.;

γ-Irradiation

Lee, K. T.; Lee, N.; Choi, Y.; Park, W.; Ling, D., Theranostic

Biomimetic

Cancer

Theranostics

Phototherapy with

UV

by

and

core–shell

SrF

2:

Yb,

Tm@

CaF

2:

Gd

Protection. Adv. Mater. 2016.

Probe Based on Lanthanide-Doped Nanoparticles for

(5). Mehrmohammadi, M.; Shin, T.-H.; Qu, M.; Kruizinga,

Simultaneous

P.; Truby, R. L.; Lee, J.-H.; Cheon, J.; Emelianov, S. Y., In vivo

Photodynamic Therapy. Adv. Mater. 2012, 24, (42), 5755-5761.

pulsed magneto-motive ultrasound imaging using high-

(15). Setua, S.; Menon, D.; Asok, A.; Nair, S.; Koyakutty, M.,

performance magnetoactive contrast nanoagents. Nanoscale

Folate receptor targeted, rare-earth oxide nanocrystals for bi-

2013, 5, (22), 11179-11186.

modal fluorescence and magnetic imaging of cancer cells.

(6). Zeng, S.; Tsang, M.-K.; Chan, C.-F.; Wong, K.-L.; Hao, J.,

Biomaterials. 2010, 31, (4), 714-729.

PEG modified BaGdF 5: Yb/Er nanoprobes for multi-modal

(16). Zhang, Y.; Lin, J. D.; Vijayaragavan, V.; Bhakoo, K. K.;

upconversion

Tan, T. T. Y., Tuning sub-10 nm single-phase NaMnF 3

fluorescent,

in

vivo

X-ray

computed


In

Vivo

Dual-Modal

Imaging

and

10

Page 11 of 12

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 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


nanocrystals as ultrasensitive hosts for pure intense

Super-paramagnetic Persistent Luminescence Nanohybrids.

fluorescence and excellent T 1 magnetic resonance imaging.

Small 2015, 11, (22), 2696-2704.

Chem. Commun. 2012, 48, (83), 10322-10324.

(28).

(17). Yang, H.; Santra, S.; Walter, G. A.; Holloway, P. H.,

Dong,

GdIII-Functionalized

as

functionalized persistent luminescent nanoparticles as a

Multimodal Imaging Probes. Adv. Mater. 2006, 18, (21), 2890-

multimodal probe for near-infrared luminescence and

2894.

magnetic resonance imaging in vivo. Anal. Chem. 2014, 86,

(18). Liu, C.; Gao, Z.; Zeng, J.; Hou, Y.; Fang, F.; Li, Y.; Qiao,

(9), 4096-4101.

R.; Shen, L.; Lei, H.; Yang, W., Magnetic/upconversion

(29).

fluorescent NaGdF4: Yb, Er nanoparticle-based dual-modal

Synthesis of mesoporous silica nanoparticles via controlled

molecular probes for imaging tiny tumors in vivo. ACS nano

hydrolysis and condensation of silicon alkoxide. Chem.

2013, 7, (8), 7227-7240.

Mater. 2009, 21, (16), 3823-3829.

(19). Wang, S.; Jarrett, B. R.; Kauzlarich, S. M.; Louie, A. Y.,

(30).

Core/shell

and

Bessodes, M.; Scherman, D., Effect of core diameter, surface

photoluminescence for multimodality imaging. J. Am. Chem.

coating, and PEG chain length on the biodistribution of

Soc. 2007, 129, (13), 3848-3856.

persistent luminescence nanoparticles in mice. ACS nano

(20).

2011, 5, (2), 854-862.

quantum

Fluorescent

dots

with

Quantum

high

Dots

relaxivity

Frangioni, J. V., In vivo near-infrared fluorescence

Abdukayum, A.; Yang, C.-X.; Zhao, Q.; Chen, J.-T.; L.-X.;

Yan,

X.-P.,

Gadolinium

complexes

Qiao, Z.-A.; Zhang, L.; Guo, M.; Liu, Y.; Huo, Q.,

Maldiney, T.; Richard, C.; Seguin, J.; Wattier, N.;

imaging. Curr. Opin. Chem. Biol. 2003, 7, (5), 626-634.

(31).

(21). de Chermont, Q. l. M.; Chanéac, C.; Seguin, J.; Pellé, F.;

Viana, B.; Gourier, D., ZnGa 2 O 4: Cr 3+: a new red long-

Maîtrejean, S.; Jolivet, J.-P.; Gourier, D.; Bessodes, M.;

lasting phosphor with high brightness. Opt. Express 2011, 19,

Scherman, D., Nanoprobes with near-infrared persistent

(11), 10131-10137.

luminescence for in vivo imaging. Proc. Natl. Acad. Sci. 2007,

(32).

104, (22), 9266-9271.

Kouadri-Boudjelthia, E. A.; Alahrache, S.; Porcher, F.;

(22). Weissleder, R.; Ntziachristos, V., Shedding light onto

Massiot, D.; Fayon, F., Considerable improvement of long-

live molecular targets. Nat. Med. 2003, 9, (1), 123-128.

persistent luminescence in germanium and tin substituted

(23). Smith, A. M.; Mancini, M. C.; Nie, S., Second window

ZnGa2O4. Chem. Mater. 2013, 25, (9), 1600-1606.

for in vivo imaging. Nat. Nanotechnol. 2009, 4, (11), 710-711.

(33). Wang, F.; Deng, R.; Wang, J.; Wang, Q.; Han, Y.; Zhu,

(24). Tavares, A. J.; Chong, L.; Petryayeva, E.; Algar, W. R.;

H.; Chen, X.; Liu, X., Tuning upconversion through energy

Krull, U. J., Quantum dots as contrast agents for in vivo

migration in core–shell nanoparticles. Nat. Mater. 2011, 10,

tumor imaging: progress and issues. Anal. Bioanal. Chem.

(12), 968-973.

2011, 399, (7), 2331-2342.

(34). Shi, J.; Fu, H.; Sun, X.; Shen, J.; Zhang, H., Magnetic,

(25). Nonat, A.; Chan, C. F.; Liu, T.; Platas-Iglesias, C.; Liu,

long persistent luminescent and mesoporous nanoparticles

Z.; Wong, W.-T.; Wong, W.-K.; Wong, K.-L.; Charbonnière,

as trackable transport drug carriers. J. Mater. Chem. B 2015, 3,

L. J., Room temperature molecular up conversion in solution.

(4), 635-641.

Nat. Commun. 2016, 7, 11978.

(35). Basavaraju, N.; Priolkar, K. R.; Gourier, D.; Bessière, A.;

(26). Lécuyer, T.; Teston, E.; Ramirez-Garcia, G.; Maldiney,

Viana, B., Order and disorder around Cr 3+ in chromium

T.; Viana, B.; Seguin, J.; Mignet, N.; Scherman, D.; Richard,

doped persistent luminescent AB 2 O 4 spinels. Phys. Chem.

C.,

Chem. Phys. 2015, 17, (16), 10993-10999.

Chemically

engineered

persistent

luminescence

Bessière, A.; Jacquart, S.; Priolkar, K.; Lecointre, A.;

Allix, M.; Chenu, S. b.; Véron, E.; Poumeyrol, T.;

nanoprobes for bioimaging. Theranostics 2016, 6, (13), 2488.

(36).

(27). Teston, E.; Lalatonne, Y.; Elgrabli, D.; Autret, G.; Motte,

Functional near infrared-emitting Cr3+/Pr3+ co-doped zinc

L.; Gazeau, F.; Scherman, D.; Clément, O.; Richard, C.;

gallogermanate persistent luminescent nanoparticles with

Maldiney, T., Design, Properties, and In Vivo Behavior of

superlong afterglow for in vivo targeted bioimaging. J. Am.

Abdukayum, A.; Chen, J.-T.; Zhao, Q.; Yan, X.-P.,

Chem. Soc. 2013, 135, (38), 14125-14133.


11


Page 12 of 12

(37). Li, Y.-J.; Yan, X.-P., Synthesis of functionalized triple-

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 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

doped zinc gallogermanate nanoparticles with superlong near-infrared persistent luminescence for long-term orally administrated bioimaging. Nanoscale 2016, 8, (32), 1496514970. (38).

Shi, J.; Sun, X.; Zhu, J.; Li, J.; Zhang, H., One-step

synthesis of amino-functionalized ultrasmall near infraredemitting persistent luminescent nanoparticles for in vitro and in vivo bioimaging. Nanoscale 2016, 8, (18), 9798-9804.

Table of Contents

3+

Gd -based NIR persistent luminescence multimodal probe ZGOCS@MSNs@Gd2O3 for MRI and NIR persistent luminescence imaging was successfully synthesized using MSNs as the reaction vessels. This multifunctional nanosphere not only preserves excellent NIR persistent luminescence properties with rechargeable ability, but also possesses high longitudinal relaxivity via the Gd2O3 shell.


12

Magnetic-NIR Persistent Luminescent Dual-Modal ... - ACS Publications

Recommend Documents