Facile Fabrication of Rare-Earth-Doped Gd2O3 Hollow Spheres with

Oct 31, 2011 - F. Karely Chamé , M. Miguel Ojeda , G. Federico González , Víctor M. Rentería T. , M. Ma. ... Sung Jun Park , Jin Young Park , Hyun...
0 downloads 0 Views 4MB Size
Download PDF
ARTICLE pubs.acs.org/JPCC

Facile Fabrication of Rare-Earth-Doped Gd2O3 Hollow Spheres with Upconversion Luminescence, Magnetic Resonance, and Drug Delivery Properties Gan Tian,†,§ Zhanjun Gu,*,† Xiaoxiao Liu,† Liangjun Zhou,†,|| Wenyan Yin,† Liang Yan,† Shan Jin,†,|| Wenlu Ren,† Gengmei Xing,† Shoujian Li,§ and Yuliang Zhao*,†,‡ †

)

Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049, People's Republic of China ‡ Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanosciences and Technology of China, Beijing, 100190, China § College of Chemistry, Sichuan University, Chengdu, 610064, People's Republic of China College of Materials Science and Opto-Electronic Technology, Graduate University of Chinese Academy of Sciences, Beijing, 100049, People's Republic of China

bS Supporting Information ABSTRACT: Rare-earth (RE)-doped gadolinium oxide (Gd2O3) hollow nanospheres have been successfully prepared on a large scale via a template-directed method using hydrothermal carbon spheres as sacrificed templates. Scanning electron microscope and transmission electron microscope images reveal that these hollow-structured nanospheres have the mesoporous shells that are composed of a large amount of uniform nanoparticles. By doping the RE ions (Yb/Er) into the Gd2O3 host matrix, these NPs emitted bright multicolored upconversion emissions that can be fine-tuned from green to red by adjusting the codoped Yb/Er ratio under 980 nm NIR laser excitation. The possibility of using these upconversion nanoparticles for optical imaging in vivo has been demonstrated. It was also shown that these Gd2O3 nanospheres brightened the T1-weighted images and enhanced the r1 relaxivity of water protons, which suggested that they could act as T1 contrast agents for magnetic resonance (MR) imaging. Moreover, these hollow spheres can be used as drug delivery host carriers, and drug storage/release properties were investigated using ibuprofen as the model drug. As a result, the so-prepared nanoscaled Gd2O3 hollow spheres bearing upconversion luminescence, MR imaging, and drug delivery capabilities could be potentially employed for simultaneous MR/fluorescent imaging and therapeutic applications.

1. INTRODUCTION Recently, multifunctional nanomaterials are at the forefront of the scientific research field due to their unique properties and their potential applications in different fields. In particular, for biomedical applications, multifunctional nano-objects are able to combine two or more functions, such as different types of imaging or imaging with drug delivery, targeting, or various therapies. In recent years, the development of inorganic multifunctional nanoplatforms combining distinct magnetic and fluorescent nanoparticles as well as mesoporous/hollowed structures in a single nano-object have been receiving great attention, since these materials hold great promise for biomedical applications, such as diagnostic analysis, MR imaging, fluorescent labeling, and drug delivery carriers.1 5 On the one hand, the combination of magnetic and fluorescent properties yields dual-imaging probes that can provide bifunctionalities of high sensitivity/resolution fluorescence imaging, as well as noninvasive and high spatial resolution MR imaging for real-time monitoring.6 10 On the other hand, mesoporous structures, especially hollow spherical particles with mesoporous shells, are of special interest since they r 2011 American Chemical Society

combine the characteristics of both macroporous and mesoporous structures in one single unit.11 16 The hollow cavity in the particles can store the cargos, whereas the mesoporous shell provides controlled release pathways for encapsulated substances.17 19 Therefore, combining magnetic and optical properties within such a hollow nano-object will enable the development of multifunctional nanomedical platforms for simultaneous imaging diagnosis and drug delivery. However, it is apparent that introducing two or more kinds of magnetic/ fluorescent nanoparticles (NPs) into one nanosystem is complex and difficult. Thus, the development of a single-phase multifunctional nanoparticle that works by itself without adding any other moieties is a better choice for such a purpose. From this point of view, gadolinium oxide (Gd2O3) nanoparticles are attractive, promising single-phase multifunctional bioprobes that present a combination of magnetic and optical properties within one particle.20 22 Gd2O3 NPs have been Received: September 19, 2011 Revised: October 28, 2011 Published: October 31, 2011 23790

dx.doi.org/10.1021/jp209055t | J. Phys. Chem. C 2011, 115, 23790–23796

The Journal of Physical Chemistry C approved as effective T1 MR imaging contrast agents because Gd3+ ions possess a large number of unpaired electrons. Moreover, Gd2O3 is also a good host matrix for luminescent rare-earth (RE) ions to fabricate downconversion (DC) or upconversion (UC) phosphors, which has been proven promising for applications in vitro/in vivo optical imaging. It is worth noting that UC luminescent probes have considerable advantages over the conventionally used fluorescent dyes and quantum dots.23 26 Compared with these traditional fluorescent labels, UC NPs can be excited by 980 nm NIR radiation with an excellent signal-to-noise ratio owing to the absence of autofluorescence and reduction of light scattering. Therefore, RE ion-doped Gd2O3 UC NPs are a very attractive choice for achieving a single-phase multimodality nanoprobe (i.e., paramagnetism and multicolored upconversion emissions). However, to the best of our knowledge, the synthesis and biomedical application of hollow-structured Gd2O3 nanospheres combining both UC fluorescent property and MR imaging modality have not been realized so far. In the present study, we have utilized a homogeneous precipitation method to fabricate nanoscaled Gd2O3 hollow spheres with a mesoporous shell using urea as a precipitating agent and hydrothermal carbon spheres (HTCs) as a hard template, followed by a further heat treatment. The formation process, structure, and morphology of the hollow spheres were investigated in detail. By codoping upconverting RE ions (Yb/Er) into the Gd2O3 host matrix, we were able to synthesize an effective multimodal imaging probe with upconversion luminescence (UCL) and magnetic characters. Furthermore, considering the storage ability of the hollow-structured materials, these hollow spheres were also studied as a drug carrier by using IBU as the model drug.

2. EXPERMENTAL SECTION Materials. Gd(NO3)3 3 6H2O (99.9%), Yb(NO3)3 3 xH2O (x ≈ 5; 99.99%), Er(NO3)3 3 xH2O (x ≈ 5; 99.9%), 4-isobutyl-αmethylphenyacetic acid (IBU, 99%), glucose (99%), and urea (98%) were all supplied by Alfa Aesar Reagent Company and used without further purification. Ethanol and hexane purchased from Beijing Chemical Corporation were of analytical reagent grade and used as received. Preparation of Hydrothermal Carbon Spheres (HTCs). The carbon nanosphere templates were prepared through the polycondensation reaction of glucose under hydrothermal conditions.27 In a typical procedure, glucose (2 g) was dissolved in 30 mL of deionized water to form a clear solution. The solution was then sealed in a 40 mL Teflon-lined autoclave and maintained at 200 °C for 5 h. After the autoclave was naturally cooled to room temperature, the resulting black-brown precipitates were collected by centrifugation, washed several times with ethanol and deionized water, and dried in a vacuum oven at 60 °C for 8 h. Fabrication of Hollow Gd2O3 and Gd2O3:Yb/Er Nanospheres. In a typical synthesis, 2 mL of 0.5 M Gd(NO3)3 aqueous solution was added into a 50 mL round-bottom flask and dissolved in a mixed solvent of ethanol and water (10 mL of ethanol and 10 mL of water) to form a clear solution. A 0.6 g portion of urea was then added into the metal solution under vigorous stirring. After stirring for 5 min, the as-prepared dried hydrothermal carbon spheres (0.10 g) were added and well dispersed into the above solution with the assistance of sonication for 15 min. Subsequently, the flask containing the mixture was placed in a water bath and heated at 90 °C for 6 h under

ARTICLE

vigorous stirring. The product was isolated by centrifugation and washed with deionized water and ethanol three times and dried at 60 °C in air. The final hollow Gd2O3 spheres were obtained through a heat treatment at 800 °C for 2 h with a heating rate of 2 °C/min under an air atmosphere. A similar process was employed for preparing hollow Gd2O3: Yb/Er upconversion nanophosphors by using a stoichiometric amount of Yb(NO3)3 and Er(NO3)3 aqueous solutions instead of Gd(NO3)3 solution at the initial stage as described above. Characterizations. X-ray powder diffraction (XRD) analyses were performed using a Japan Rigaku D/max-2500 X-ray powder diffractometer with Cu Kα radiation (λ = 1.54 Å). The morphologies and composition of the samples were obtained by a field emission scanning transmission electron microscope (FESEM, Hitachi S-4800) equipped with an energy-dispersive X-ray spectroscope (EDX, Horiba 7593-H model). Transmission electron microscope (TEM) observations were performed with an FEI Tecnai G2 S-Twin instrument operated at 200 kV. Fourier transform infrared (FTIR) spectra were recorded on a Bruker EQUINOX55 spectrometer with a potassium bromide (KBr) pellet technique. The UV vis absorption spectral data were measured using a TU-1901 spectrophotometer. Nitrogen adsorption desorption analysis was performed with a Micromeritics ASAP 2020 (M + C) apparatus, and the specific surface area was determined by the Brunauer Emmett Teller (BET) method. UC emission spectra were obtained using a Horiba Jobin Yvon FluoroLog3 spectrometer equipped with a 980 nm NIR laser as the excitation source. Upconversion luminescent photographs were taken with a Nikon D3100 digital camera. The quantification of cell viability was determined using an ELISA microplate reader (Spectra Max M2, USA) at an optical absorbance of 450 nm. In Vitro Cytotoxicity Test. To assess the cytotoxity of the Gd2O3:Yb/Er nanoprobes, A549 cells (human epithelial lung cancer) were grown in the presence of hollow Gd2O3:Yb/Er nanospheres, and the viability was measured using a CCK-8 assay. Cells were cultured in a 96-well microplate (approximately 2000 cells per well) with a medium containing various concentrations of Gd2O3:Yb/Er spheres for 24 h at 37 °C in a humid atmosphere of 95% air and 5% CO2. After the culture medium was removed, 100 μL of fresh culture medium (DMEM) containing 10% CCK-8 reagent was added to each well and the cells were incubated at 37 °C for an additional 2 h. The quantification of cell viability was determined using an ELISA microplate reader at an optical absorbance of 450 nm. The cell viability was calculated as the ratio of the absorbance of the sample well to that of the control well and expressed as a percentage. In Vivo Animal Imaging. A three-week old Kunming mouse was placed under anesthesia using ether for in vivo studies. The Gd2O3:Yb/Er hollow spheres that emit red emission were chosen as the fluorescent probe, and they were dispersed in PBS solution (pH 7.4). For deep tissue imaging, the Kunming mouse was, respectively, injected subcutaneously at the foot, back, and upper leg regions with 100 μL of the Gd2O3:Yb/Er dispersion (3 mg/mL). The depth of injection was estimated from needle penetration. UCL was observed in a darkened room by excitation with a 980 nm laser and recorded using a CCD-based digital camera (Nikon) with an 800 nm short-pass filter to eliminate NIR scatter. At the end of the experiments, the animals were disposed of according to the standard protocol approved by the 23791

dx.doi.org/10.1021/jp209055t |J. Phys. Chem. C 2011, 115, 23790–23796

The Journal of Physical Chemistry C

ARTICLE

Scheme 1. Schematic Illustration for the Overall Fabrication Process of Gd2O3 Hollow Spheres

Figure 2. SEM images of (a) as-prepared hydrothermal carbon sphere templates, (b) uncalcined core shell structured precursor, and (c, d) Gd2O3 hollow spheres. Inset: TEM image of Gd2O3 hollow spheres.

Figure 1. XRD patterns of (a) as-formed core shell structured precursor, (b) pure Gd2O3, and (c)Yb/Er-codoped Gd2O3 after calcination at 800 °C for 2 h.

Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety (Institute of High Energy Physics, CAS). Relaxivity Measurement. The T1-weighted MR images were obtained using a 4.7 T MR imaging instrument (Biospec; Bruker, Ettlingen, Germany). Despersions of Gd2O3 hollow spheres (0.05, 0.10, 0.20, 0.50, 1.0 mM) in 0.5% agarose gel were placed in a series of 1.5 mL NMR tubes for T1-weighted MR imaging. The measurement was performed running a standard multislice and multiecho sequence with a repetition time (TR) of 400 ms, an echo time (RE) of 11 ms, the inversion time (TI) from 23 to 9000 ms, and the number of excitations (NEX) of 8. The acquired images had a matrix size of 128  128, a field of view of 40  40 mm, and a slice thickness of 1.20 mm. Drug Storage/Delivery Systems. The drug storage/release system using the hollow Gd2O3:Yb,Er spheres as a drug carrier was prepared according to the previous reports with a small modification, and ibuprofen (IBU) was selected as the model drug.1 Typically, 50 mg of the Gd2O3:Yb/Er sample was added into 10 mL of a hexane solution with an IBU concentration of 20 mg/mL at room temperature and soaked for 24 h with stirring in a vial that was sealed to prevent the evaporation of hexane. The IBU-loaded sample was separated by centrifugation and then dried in vacuum at 60 °C for 12 h to obtain IBU-Gd2O3 powder. The IBU-Gd2O3 sample was then transferred to a conical flask and immersed in 10 mL of phosphate buffer solution (PBS) with slow shaking at 37 °C. At selected time intervals, a certain amount of PBS was removed and immediately replaced with an equal volume of fresh PBS. The amounts of released IBU in the supernatant solutions were measured at 220 nm by a UV vis spectrophotometer.

3. RESULTS AND DISCUSSION Formation Process, Phase Structure, and Morphology. In this work, the homogeneous precipitation route was adapted to

prepare hollow Gd2O3 spheres using HTCs as the sacrificed templates. The whole synthesis process can be illustrated in Scheme 1. The HTCs are chosen as the sacrificed template due to their facile removal and their core shell structure composed of a hydrophobic core and a stabilizing hydrophilic shell that contains a large number of reactive oxygen functional groups.27 The hydrophilic functional oxygen-containing groups provide a good affinity with Gd3+ and adsorb them onto the HTCs' surface to induce in situ formation of another shell composed of Gd(OH)CO3 when OH and CO32 were released from urea at high temperature. During the calcination procedure, the HTC templates were burned up and the amorphous Gd(OH)CO3 shells were decomposed and converted into crystalline Gd2O3 nanoparticles, resulting in the formation of the hollow Gd2O3 spheres. Figure 1, patterns a c, shows the X-ray diffraction (XRD) patterns of the as-prepared precursor, the pure Gd2O3 and Yb/Er-codoped Gd2O3 after calcination at 800 °C for 2 h, respectively. It can be seen that no obvious diffraction peak appears for the precursor (Figure 1, pattern a), indicating that it is amorphous before calcination. After annealing at 800 °C for 2 h, all the diffraction peaks of the pure and Yb/Er-codoped products (Figure 1, patterns b and c) can be directly indexed as the cubic phase of Gd2O3 (JCPDS No. 12-0797). Moreover, we find that the diffraction peaks of Yb/Er-codoped Gd2O3 shift slightly to the higher-angle side compared with those of the undoped Gd2O3, which can be related to the smaller ionic radius of the doped rare-earth ions.28 SEM and TEM were utilized to characterize the morphology and structure of as-prepared samples. Figure 2a shows an SEM image of the as-prepared HTCs. It can be seen that the sample consists of well-dispersed microspheres with a smooth surface and a narrow size distribution in the range of 200 250 nm. After the homogeneous precipitation, as shown in Figure 2b, the spherical morphology of the precursor still remained unchanged except for a slightly larger particle size due to the loaded Gd(OH)CO3 shell. Additionally, it should be noted that the precursor exhibits a much rougher surface than that of the bare HTC spheres due to the formation of an amorphous shell that was composed of a large number of nanoparticles. Figure 2c,d shows the morphology of the Gd2O3 sample after calcination at 800 °C. A panoramic SEM image demonstrates that there exists large-scale uniform Gd2O3 hollow spheres (Figure 2c), which implies that the HTC templates essentially determine the shape 23792

dx.doi.org/10.1021/jp209055t |J. Phys. Chem. C 2011, 115, 23790–23796

The Journal of Physical Chemistry C and size of the final products. In addition, it is clearly shown that the average diameter of the Gd2O3 hollow spheres decreases in comparison with that of the precursor. The shrinkage can be attributed to the dehydration of the cross-linked structure of HTCs templates and the crystallization of the Gd2O3 phase from the loosely covered precursor during the calcination process. The ruptured hollow spheres (Figure 2d) indicate that the Gd2O3 spheres are of hollow structures, and the shell thickness is about 20 nm, which could be further confirmed by the TEM results (inset in Figure 2d). The holes of the rupture hollow spheres should be caused by the CO2 releasing when the HTC templates burn up during the annealing process. To investigate the specific surface area and porous nature of the Gd2O3 hollow spheres, nitrogen sorption measurements were conducted. Figure 3 shows the N2 adsorption desorption isotherm and pore size distribution of the as-prepared Gd2O3: Yb/Er sample. As shown in Figure 3, the isotherm is Type II and characteristic of a macroporous material that exhibits a significant rise at high P/P0 values.29 The Brunauer Emmett Teller (BET) surface area is about 33.39 m2/g, and the pore volume is 0.173 cm3/g, which is not particularly large since the material is predominately macroporous with thin shells. However, the presence of hysteresis in the adsorption desorption branch

Figure 3. N2 adsorption desorption isotherm of Yb/Er-codoped Gd2O3 hollow spheres. Inset: the pore size distribution curve obtained from the adsorption data.

ARTICLE

reveals the existence of mesoporosity in the sample.30 A plot of the pore size distribution, calculated using the Barrett Joyner Halenda (BJH) distribution from the adsorption branch, shows a narrow apex centered at 10.9 nm. The mesopores are possibly attributable to the holes of the ruptured hollow spheres caused by the released CO2, which is in agreement with SEM observations (Figure 2d). This result confirms that the as-obtained Gd2O3: Yb/Er hollow spheres have porous structures and may offer potential application in drug delivery system. The Yb/Er-codoped precursor and final product were taken as an example to investigate the element composition by energydispersive X-ray (EDX) spectra. The EDX analysis indicates that the HTC templates have been removed completely and the precursor shell has converted to crystalline Gd2O3 during the calcination process (Figure S1 in the Supporting Information). In addition, Fourier transform infrared (FT-IR) spectra were used to identify the functional groups of the HTC templates, the core shell-structured precursor, and the final Gd2O3 product (Figure S2 in the Supporting Information). The FT-IR results provide additional evidence that the HTC templates can be effectively removed after calcination, which agrees well with the XRD and EDX results. The detailed discussion of the EDX and FT-IR analyses is presented in the Supporting Information. Upconversion Luminescence Studies. The UCL spectra of the Yb/Er-codoped Gd2O3 hollow spheres are shown in Figure 4a. Upon excitation at 980 nm, the Gd2O3 hollow spheres codoped with Yb/Er exhibit characteristic sharp emission peaks, which can be attributed to 2H11/2, 4S3/2 f 4I15/2, and 4F9/2 f 4 I15/2 transitions of Er3+ ions.31 These peaks correspond to respective green and red emissions that result in the manipulation of the emission color output from green to red by varying the Yb3+ doping level (Figure 4a, inset). Introducing an elevated amount of Yb3+ dopants in the Gd2O3 host lattice would decrease the Yb 3 3 3 Er interatomic distance and thus facilitate back-energy-transfer from Er3+ to Yb3+.32 The energy transfer, 4 F7/2 (Er) + 2F7/2 (Yb) f 4I11/2 (Er) + 2F5/2 (Yb), should depopulate the excited 4F7/2 level and subsequently suppress the population in excited levels of 2H11/2 and 4S3/2, resulting in the decrease of the green (2H11/2, 4S3/2 f 4I15/2) light emissions. In that case, upon doping with increased concentrations of Yb3+, the ratio of red to green emission should increase correspondingly

Figure 4. (a) Upconversion luminescence spectra of Yb/Er-codoped Gd2O3 under different Yb/Er doping levels. Inset: the corresponding upconversion luminescent photographs taken under 980 nm NIR excitation. (b) Energy level diagram for the upconversion emission from Yb/Ercodoped Gd2O3 under 980 nm NIR excitation. 23793

dx.doi.org/10.1021/jp209055t |J. Phys. Chem. C 2011, 115, 23790–23796

The Journal of Physical Chemistry C

ARTICLE

Figure 5. In vitro cell viability of A549 cells incubated with Yb/Ercodoped Gd2O3 hollow spheres at different concentrations for 24 h at 37 °C.

Figure 7. (a) Relaxation rate R1 (1/T1) versus various molar concentrations of Gd2O3 NPs dispersions at room temperature using a 4.7 T MRI scanner. (b) T1-weighted images of various molar concentrations of Gd2O3 NPs.

Figure 6. In vivo upconversion luminescence imaging of Kunming mouse: Yb/Er-codoped Gd2O3 spheres injected into (a) translucent skin of foot, (b) below skin of back, and (c) thigh muscles show red luminescence.

and realize a color output from green to red. In addition, to determine the number of photons responsible for the UC mechanism, the intensities of the UCL were recorded as a function of the 980 nm excitation intensity (Figure S3 in the Supporting Information). It can be seen that, for all the emissions, the slopes are the typical values of 1.5 2.5, indicating that the population of the states 4S3/2 and 4F9/2 comes from the twoor three-photon UC processes, respectively. Figure 4b shows a typical energy level diagram of the Er3+and Yb3+ ions as well as the probable UC mechanism accounting for the green and red emissions under 980 nm NIR excitation. UCL imaging in vivo is expected to be the next-generation optical imaging technique because it provides a high sensitivity and spatial resolution.23 More importantly, it could lead to predictive models for potential clinical applications.7 Before in vivo imaging, a CCK-8 assay with A549 cells was performed on the Gd2O3:Yb/Er hollow spheres to evaluate their cytotoxicity. Figure 5 shows the cell viability results, which indicate that a more than 90% cell viability was observed under a varying concentration range. This result clearly demonstrated the satisfactory biocompatibility of the hollow spheres in all dosages, indicating that they could serve as a potential probe for fluorescent imaging. Gd2O3:Yb/Er hollow spheres that emit a red emission were chosen as the luminescent probes since both the excitation and the emission wavelengths of the particles fall within the “optical widow” of biotissue (650 1000 nm) and thus permit the deep tissue penetration.23,33 The red-emitting spheres dispersed in phosphate buffered saline (PBS, 3 mg/mL) were subcutaneously injected into the foot, back, and thigh of a mouse and then examined by in vivo optical imaging. UCL images in Figure 6 revealed that the red emission signals could

Figure 8. FT-IR spectra of (a) pure IBU and (b) IBU-Gd2O3.

easily penetrate these tissues and provide high-contrast UCL imaging. This study clearly demonstrates the advantages of UC NPs for in vivo imaging for which the 980 nm NIR irradiation minimizes the autofluorescence background and the upconversion luminescence is spectrally separated from biological autofluorescence of the mouse tissue. In addition, this demonstration of in vivo UCL imaging opens the possibility for future use of this material platform for angiography, intraoperative imaging, or other bioimaging applications. Relaxivity Measurement. MR imaging is one of the most powerful and noninvasive diagnostic techniques for living organisms based on the interaction of protons with the surrounding molecules of tissues. The use of MR contrast agents can help to clarify images and allow better interpretation.4 Recently, Gdcontaining particles have potential as MR imaging contrast agents because of their positive signal-enhancement ability.6 10 To evaluate the potential application of Gd2O3 hollow spheres as MR imaging contrast agents, T1 relaxatiom time was measured in aqueous dispersions with different Gd3+ concentrations. The longitudinal relaxivity (r1) was estimated to be 2.78 s 1 mM 1 23794

dx.doi.org/10.1021/jp209055t |J. Phys. Chem. C 2011, 115, 23790–23796

The Journal of Physical Chemistry C

ARTICLE

Figure 9. (a) The UV absorbance spectra of IBU/hexane solutions before and after interaction with Gd2O3:Yb/Er hollow spheres. (b) Cumulative IBU release from IBU-Gd2O3:Yb/Er as a function of release time in PBS.

from the slope of the relaxation rate (1/T1) as a function of Gd3+ concentration (Figure 7a). In a proof-of-concept application as MR imaging contrast agents (Figure 7b), representative T1weighted MR images of the Gd2O3 suspensions clearly showed positive signal enhancement of the effect on T1-weighted sequences as the Gd3+ concentration increased, resulting in brighter images. These results suggest that the as-prepared Gd2O3 hollow spheres could be employed as an effective T1 contrast agent. Drug Adsorption and Release Properties. Ibuprofen (IBU) was selected as a model drug to study the drug storage and release properties of this system. In the FT-IR spectrum of IBU-loaded Yb/Er-codoped Gd2O3 hollow spheres (IBU-Gd2O3, Figure 8, spectrum b), the absorption bands assigned to COO at 1570 cm 1, C C bonds at 1461 and 1371 cm 1, as well as C Hx bands at 2972 and 2874 cm 1 arising from the introduced IBU (Figure 8) are obvious, which confirms the successful incorporation of IBU into the Gd2O3 hollow spheres.1 The loading amount of IBU in Gd2O3 hollow spheres was determined as 175.9 mg/g based on the change of absorbance spectrometry of the IBU/hexane solution (20 mg/mL) before and after the interaction with Gd2O3 (Figure 9a). The high loading amount may be attributed to the cooperativity of the internal and external surface adsorption, and the mesoporous holes on the ruptured hollow spheres that facilitate the transport of IBU to the internal surface.34 The cumulative drug release profiles for the IBU-Gd2O3 systems as a function of release time in PBS are shown in Figure 9b. The system shows a burst release of about 60% within 0.5 h and nearly 80% within 2 h, followed by a relatively slow release and complete release after 10 h. The initial sharp burst release may be caused by the rapid leaching of IBU from the outer surface, and the slow release of the remaining of IBU may be due to adsorption on the internal surface of the hollow spheres.

4. CONCLUSIONS In summary, we have successfully prepared the uniform and well-dispersed Gd2O3 hollow spheres by a template-directed method with HTCs as templates. In vivo UCL imaging and in vitro relaxivity measurements demonstrated that the as-prepared Gd2O3:Yb/Er hollow spheres could serve as a dual-imaging agent for optical/MR imaging. Furthermore, drug storage/release properties of the Gd2O3:Yb/Er hollow spheres were investigated using an IBU model, and the good drug adsorption capability

reflected the advantages of the hollow spheres employed as drug carriers. Hence, because of the combined presence of efficient optical and MR imaging capabilities, as well as the hollow structure, these nanoprobes based on Gd2O3 hollow spheres can be considered as a promising platform for simultaneous bioimaging and drug delivery.

’ ASSOCIATED CONTENT

bS

Supporting Information. Detailed description of Figures S1 S3. This material is available free of charge via the Internet at http://pubs.acs.org.

’ AUTHOR INFORMATION Corresponding Author

*E-mail: [email protected] (Z.G.), [email protected] (Y.Z.).

’ ACKNOWLEDGMENT This work was supported by the National Basic Research Programs of China (973 program, Nos. 2012CB932504 and 2011CB933403) and the National Natural Science Foundation of China (Nos. 21001108 and 21177128). ’ REFERENCES (1) Gai, S. L.; Yang, P. P.; Li, C. X.; Wang, W. X.; Dai, Y. L.; Niu, N.; Lin, J. Adv. Funct. Mater. 2010, 20, 1166–1172. (2) Staedler, B.; Price, A. D.; Zelikin, A. N. Adv. Funct. Mater. 2011, 21, 14–28. (3) Jennings, L. E.; Long, N. J. Chem. Commun. 2009, 3511–3524. (4) Kim, J.; Piao, Y. Z.; Hyeon, T. Chem. Soc. Rev. 2009, 38, 372–390. (5) Xu, Z. H.; Ma, P. A.; Li, C. X.; Hou, Z. Y.; Zhai, X. F.; Huang, S. S.; Lin, J. Biomaterials 2011, 32, 4161–4173. (6) Park, Y.; Kim, J. H.; Lee, K. T.; Jeon, K. S.; Na, H. B.; Yu, J. H.; Kim, H. M.; Lee, N.; Choi, S. H.; Baiket, S.; et al. Adv. Mater. 2009, 21, 4467–4471. (7) Zhou, J.; Sun, Y.; Du, X. X.; Xiong, L. Q.; Hu, H.; Li, F. Y. Biomaterials 2010, 31, 3287 3295. (8) Kumar, R.; Nyk, M.; Ohulchanskyy, T. Y.; Flask, C. A.; Prasad, P. N. Adv. Funct. Mater. 2009, 19, 853–859. (9) S€oderlind, F.; Pedersen, H.; Petoral, R. M.; K€all, P.-O.; Uvdal, K. J. Colloid Interface Sci. 2005, 288, 140–148. (10) Pedersen, H.; Ojamae, L. Nano Lett. 2006, 6, 2004–2008. 23795

dx.doi.org/10.1021/jp209055t |J. Phys. Chem. C 2011, 115, 23790–23796

The Journal of Physical Chemistry C

ARTICLE

(11) Zhang, F.; Shi, Y. F.; Sun, X. H.; Zhao, D. Y.; Stucky, G. D. Chem. Mater. 2009, 21, 5237–5243. (12) Zhang, L. H.; Jia, G.; You, H. P.; Liu, K.; Yang, M.; Song, Y. H.; Zheng, Y. H.; Huang, Y. J.; Guo, N.; Zhang, H. J. Inorg. Chem. 2010, 49, 3305–3309. (13) Dhas, N. A.; Suslick, K. S. J. Am. Chem. Soc. 2005, 127, 2368–2369. (14) Wang, Y. Q.; Tang, C. J.; Deng, Q.; Liang, C. H.; Ng, D.-H. L.; Kwong, F. L.; Wang, H. Q.; Cai, W. P.; Zhang, L. D.; Wang, G. Z. Langmuir 2010, 26, 14830–14834. (15) Lin, C. N.; Huang, M. H. J. Phys. Chem. C 2009, 113, 925–929. (16) Du, D. J.; Cao, M. H. J. Phys. Chem. C 2008, 112, 10754–10758. (17) Shin, J.; Anisur, R. M.; Ko, M. K.; Im, G. H.; Lee, J. H.; Lee, I. S. Angew. Chem., Int. Ed. 2009, 48, 321–324. (18) Wei, W.; Ma, G. H.; Hu, G.; Yu, D.; Mcleish, T.; Su, Z. G.; Shen, Z. Y. J. Am. Chem. Soc. 2008, 130, 15808–15810. (19) Zhou, J.; Wu, W.; Caruntu, D.; Yu, M. H.; Martin, A.; Chen, J. F.; O’Connor, C. J.; Zhou, W. L. J. Phys. Chem. C 2007, 111, 17473–17477. (20) Huang, C. C.; Su, C. H.; Li, W. M.; Liu, T. Y.; Chen, J. H.; Yeh, C. S. Adv. Funct. Mater. 2009, 19, 249 258. (21) Das, G. K.; Heng, B. C.; Ng, S. C.; White, T.; Loo, J. S. C.; D’Silva, L.; Padmanabhan, P.; Bhakoo, K. K.; TamilSelvan, S.; Tan, T. T. Y. Langmuir 2010, 26, 8959–8965. (22) Petoral, R. M., Jr.; Soderlind, F.; Klasson, A.; Suska, A.; Fortin,  M. A.; Abrikossova, N.; Selegard, L.; Kall, P. O.; Engstrom, M.; Uvdal, K. J. Phys. Chem. C 2009, 113, 6913–6920. (23) Chatterjee, D. K.; Gnanasammandhan, M. K.; Zhang, Y. Small 2010, 6, 2781–2795. (24) Li, Z. Q.; Zhang, Y. Angew. Chem., Int. Ed. 2006, 45, 7732–7735. (25) Wang, F.; Han, Y.; Lim, C. S.; Lu, Y. H.; Wang, J.; Xu, J.; Chen, H. Y.; Zhang, C.; Liu, X. G. Nature 2011, 423, 1061–1065. (26) Li, D.; Dong, B.; Bai, X.; Wang, Y.; Song, H. W. J. Phys. Chem. C 2010, 114, 8219–8226. (27) Hu, B.; Wang, K.; Wu, L. H.; Yu, S. H.; Antonietti, M.; Titirici, M. M. Adv. Mater. 2010, 22, 813–828. (28) Yang, J.; Zhang, C. M.; Peng, C.; Li, C. X.; Wang, L. L.; Chai, R. T.; Lin, J. Chem.—Eur. J. 2009, 15, 4649–4655. (29) Zhao, B.; Collinson, M. M. Chem. Mater. 2010, 22, 4312–4319. (30) Du, X.; He, J. H. Chem.—Eur. J. 2011, 17, 8165–8174. (31) Auzel, F. Chem. Rev. 2004, 104, 139–174. (32) Wang, F.; Liu, X. G. J. Am. Chem. Soc. 2008, 130, 5642–5643. (33) Chatterjee, D. K.; Rufaihah, A. J.; Zhang, Y. Biomaterials 2008, 29, 937–943. (34) Xu, Z. H.; Cao, Y.; Li, C. X.; Ma, P. A.; Zhai, X. F.; Huang, S. S.; Kang, X. J.; Shang, M. M.; Yang, D. M.; Dai, Y. L.; et al. J. Mater. Chem. 2011, 21, 3686–3694.

23796

dx.doi.org/10.1021/jp209055t |J. Phys. Chem. C 2011, 115, 23790–23796