Template-directed synthesis, properties, and dual-modal bioapplications of multifunctional GdPO4 hierarchical hollow spheres

Template-directed synthesis, properties, and dual-modal bioapplications of multifunctional GdPO4 hierarchical hollow spheres

Applied Surface Science 475 (2019) 264–272 Contents lists available at ScienceDirect Applied Surface Science journal homepage: www.elsevier.com/loca...

4MB Sizes 0 Downloads 6 Views

Applied Surface Science 475 (2019) 264–272

Contents lists available at ScienceDirect

Applied Surface Science journal homepage: www.elsevier.com/locate/apsusc

Full Length Article

Template-directed synthesis, properties, and dual-modal bioapplications of multifunctional GdPO4 hierarchical hollow spheres ⁎

Jiayue Tian, Fangbo Zhang, Yu Han, Xi Zhao, Chunyan Chen, Cuimiao Zhang , Guang Jia

T



Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding 071002, PR China

A R T I C LE I N FO

A B S T R A C T

Keywords: GdPO4 hollow spheres Template-directed synthesis Luminescence properties Magnetic resonance imaging Drug delivery

Well-defined GdPO4 hierarchical hollow spheres have been synthesized via a novel template-directed synthesis approach with 3-aminophenol-formaldehyde resin spheres as template. The core-shell structured precursor was firstly prepared by a homogeneous precipitation and subsequent hydrothermal route. Finally, the GdPO4 hollow spheres were obtained after an annealing process in air. The phase structure, morphology, and formation process were also investigated in detail. Moreover, the as-synthesized GdPO4 hollow spheres show good biocompatibility and excellent drug loading and sustained drug release ability. Interestingly, the lanthanide activator ions doped GdPO4 hollow spheres exhibit multimodal imaging functionality for combined optical and magnetic resonance imaging (MRI). Due to the well-defined hollow structure, good biocompatibility, luminescence properties, positive magnetic signal-enhancement ability, and drug loading/release patterns, the as-obtained GdPO4 samples may be potentially applied in fields of bioimaging, drug delivery, and disease diagnosis. Furthermore, this novel synthetic strategy may pave a critical way for the preparation of other similar lanthanide orthophosphate functional materials with perfect hollow spherical structure, tunable particle sizes, and good physicochemical properties.

1. Introduction Hollow nanostructured materials with controlled dimensions and morphologies exhibit many unique properties and they have attracted considerable attention in the field of biochemistry and materials research [1,2]. These functional materials are widely applied to pharmaceutical or carrier delivery due to their multilayer/multipores, low refractive index and density, large specific surface area and good encapsulation capability, and sensitive surface permeability [3,4]. The modification of the inner and outer surfaces may improve the advantageous characteristics of hollow structures. Moreover, they also exhibit great research value in biocatalysis, waste removal, photoelectric technology, sensors, and so on [5,6]. Among various hollow structured materials, many efforts have been devoted to the synthesis and manufacture of ideal hollow spheres. The inorganic functional hollow spheres generally exhibit large voids and mesoporous shells. These properties are particularly beneficial for drug delivery because of their loading their high loading capacity and diffusibility for drug molecules [7,8]. Different synthesis methods have been developed to the design and fabrication of inorganic hollow spheres. Among them, the template-directed approach has been proved to be an effective



method to synthesize the inorganic hollow spheres with ideal structures. Regarding to this method, the target materials are coated on the surface of the template and then the template is removed by physical or chemical means [4,9–11]. Many organic or polymeric colloidal spheres such as carbon spheres, polystyrene, or melamine formaldehyde resin have been utilized as excellent spherical templates for the fabrication of hollow spheres [12,13]. The colloidal spheres can be completely decomposed and removed during the annealing process at high temperature in air. Great attention has been paid to the multifunctional nanostructures that exhibit variable capabilities in biological field, such as bioimaging, targeting, drug delivery, etc. [14–16]. In particular, the multimodal bioimaging is an emerging frontier in field of biomedicine that combines more than one imaging modality such as positron emission tomography (PET), X-ray computed tomography (CT), magnetic resonance imaging (MRI), optical imaging, and ultrasound [17,18]. For instance, the integration of MRI and optical imaging can combine the depth of in vivo imaging associated to MRI and high sensitivity and good spatial resolution for in vitro application of optical imaging [19–23]. It is worth noting that the gadolinium-based nanomaterials are considered to be promising multifunctional nanoplatforms for optical and

Corresponding authors. E-mail addresses: [email protected] (C. Zhang), [email protected] (G. Jia).

https://doi.org/10.1016/j.apsusc.2018.12.262 Received 9 October 2018; Received in revised form 25 December 2018; Accepted 27 December 2018 Available online 28 December 2018 0169-4332/ © 2018 Elsevier B.V. All rights reserved.

Applied Surface Science 475 (2019) 264–272

J. Tian et al.

of the Tb(NO3)3 or Eu(NO3)3 instead of Gd(NO3)3 aqueous solution at the initial stage. The materials characterizations for the precursor and products are shown in the Supplementary material.

MRI imaging within one object. Firstly, gadolinium-based materials have the potential as T1-enhanced MRI contrast agent due to a large number of unpaired electrons of Gd3+ [19,24,25]. On the other hand, the gadolinium-based compounds including GdPO4, GdVO4, Gd2O3, etc. have been intensively used as eminent matrix for rare earth activator ions. These luminescent materials exhibit some advantages for biological luminescent labels, such as low toxicity, blinking and photochemical degradation, high resistance to photobleaching, etc. [26–28]. In particular, lanthanide activator ions doped gadolinium orthophosphate (GdPO4) have been extensively studied due to its multimodal imaging and potential applications on medical biological labels [18,23,29]. To date, a variety of GdPO4 nano/microstructures with diverse morphologies have been prepared, such as nanocrystals [18], nanorods [19,29], nanocubes [23], lance-shaped crystals [30], and core-shell structures [28]. Among various nano/microstructures, the GdPO4 hollow spheres have gained considerable attentions in the field of drug storage and release due to their high surface-to-volume ratio, low density, low coefficients of thermal expansion, and good permeability. These unique characteristics may make them exhibit high drug loading capacity and sustained release patterns. As we know, the GdPO4 hollow spheres that may be potentially applied as drug carrier with multimodal imaging functionality have been generally synthesized by a self-sacrificing route with Gd(OH)CO3 as template [31]. The particle size of the hollow spheres is determined by the size of the spherical template. For the as-reported synthesis route, only one size of GdPO4 hollow spheres can be obtained due to the unalterable size of Gd (OH)CO3 template, which may limit their applications in biomedical fields. Recently, Zhao et al. developed a template-free and surfactantfree route for the fabrication of a series of uniform and well-dispersed phenol formaldehyde resin with excellent size tunability in a broad range of 80 nm to 2.5 μm [32,33]. The as-synthesized resin spheres may be applied as an excellent template to fabricate various ideal hollow spherical materials with tunable particle sizes. To our knowledge, there have been few reports for the preparation of uniform GdPO4 hollow spheres with organic or polymeric colloidal spheres as template. In the present study, well-defined GdPO4 hierarchical hollow spheres have been prepared via a novel template-directed synthesis approach with APF resin spheres as template. The morphology, crystal structure, formation process, luminescent and magnetic properties, biocompatibility, and drug loading/release behaviors of the GdPO4 hierarchical hollow spheres were investigated in detail. The as-synthesized materials may serve as a multifunctional platform for applications of bioimaging and drug delivery.

2.2. Biocompatibility and drug loading and release profiles In vitro cytotoxicity tests were conducted against with MDA-MB231 and BT474 cells by conducting MTT (3-[4,5-dimethylthiazol-2-yl]-2,5diphenyltetrazolium bromide) assays according to our previous literatures [8,34]. For details, see the Supplementary material. In this work, we selected ibuprofen (IBU) as a model drug to investigate the drug-loading and release behaviors of the GdPO4 hollow spheres. Typically, 1.75 g of ibuprofen (IBU) was mixed with 25 mL of n-hexane solution and sonicated for 5 min. Then, 0.2 g of GdPO4 hollow spheres was dispersed to the above solution. The bottle was sealed to prevent the evaporation of the solvent, and then the mixed-solution was stirred in constant temperature water at 37 °C for 24 h. The resulting IBU loaded GdPO4 sample (IBU-GdPO4) was obtained by centrifugation and vacuum dried at 60 °C for 12 h. Then, 0.1 g of the above sample with medicine flake was put into a dialysis bag containing 3 mL of the simulated body fluid (SBF), whose composition was similar to that of human body plasma (pH 7.40) [35]. The dialysis bag was placed at a centrifuge tube containing 27 mL of SBF, and then the tube was placed in a thermostatic oscillator with 37 °C for the in vitro release of ibuprofen. At predetermined time intervals, 1 mL of the sample was withdrawn from the solution and replaced by an equal volume of fresh SBF. IBU concentrations were analyzed with a UV–visible spectrophotometer at a wavelength of 222 nm. 3. Results and discussion Fig. 1a shows the XRD pattern of the as-prepared precursor treated with a homogeneous precipitation process. No obvious diffraction peak is detected except for a broad band from 15° to 60°, indicating that the precursor is amorphous. As confirmed from the previous literatures [13,33,36], the composition of the precursor is amorphous Gd(OH)CO3. When the precursor was treated with NH4H2PO4 by a hydrothermal process, the diffraction peaks (Fig. 1b) of the product can be well indexed to the hexagonal phase of gadolinium orthophosphate [GdPO4, JCPDS Card No. 39-2032, Space group: P3121 (152)]. After annealing at 500 °C, the XRD pattern (Fig. 1c) can also agree well with GdPO4 with hexagonal phase [31]. Moreover, the diffraction peaks of the Gd2O3 cannot be detected, indicating that the coating Gd(OH)CO3 precursor has been completely transformed to GdPO4 during the hydrothermal process [13]. The EDX spectrum of the calcined GdPO4 sample confirms the existence of gadolinium (Gd), phosphorus (P), and oxygen (O) elements (Fig. 1d), which can also verify the formation of GdPO4 and agree with the XRD patterns. The TG-DSC curves of the pure APF template and [email protected] are shown in Fig. S1 in the Supplementary material. One can observe from Fig. S1a that the weight loss of the pure APF resin is nearly 100%. The result reveals that the APF resin can be eliminated completely during the annealing process in air, indicating that the as-synthesized APF resin is suitable for the template-directed synthesis of the hollow spherical materials. The sharp weight loss from 200 to 650 °C is caused by the dehydration, densification, and removal of the APF resin template (Fig. S1b), which is in good accordance with the DSC curve (inset in Fig. S1). The residual weight percentage of the hydrothermal precursor is about 50%, which accounts for the final GdPO4 hollow spheres. One of the main advantages of this synthesis route is the high yield synthesis, which is effectively supported by the TG result. In order to examine the components of the samples, the FT-IR spectra were measured to characterize the functional groups. The FT-IR spectrum of the APF template (Fig. 2a) indicates that the sample exhibit characteristic absorption peaks of the APF resin. The absorption bands range from 500 to 1000 cm−1 are due to the out-of-plane CeH

2. Experimental section 2.1. Preparation of GdPO4 hierarchical hollow spheres The monodisperse APF resin template was synthesized according to previous literature with some modifications [32]. Subsequently, the [email protected](OH)CO3 precursor was synthesized by a urea-based homogeneous precipitation process. The detailed experimental procedures for APF and [email protected](OH)CO3 are demonstrated in the Supplementary material. The above [email protected](OH)CO3 precursor was dispersed in 25 mL of deionized water by ultrasonication to form a homogeneous solution. Then, 0.1150 g of NH4H2PO4 was dissolved in 10 mL of H2O followed by adding to the above solution dropwise. After stirring for 10 min, 0.1333 g of CTAB as a surface modifier was added to the above solution, and then transferred into a 50 mL autoclave and heated at 180 °C for 12 h. The as-obtained product ([email protected]) was separated by centrifugation, washed with deionized water and ethanol successively, and dried in air. Finally, the [email protected] was annealed at 500 °C for 2 h to obtain the GdPO4 hierarchical hollow spheres. The GdPO4:Tb3+ and GdPO4:Eu3+ hollow spheres were also fabricated by a similar synthesis procedure except for adding a stoichiometric amount (molar ratio, 5%) 265

Applied Surface Science 475 (2019) 264–272

J. Tian et al.

1074 cm−1 is ascribed to the asymmetry stretching vibrations of the PO43− groups, respectively. The formation of the characteristic bands of the phosphate (PO43−) groups reveals that GdPO4 has been effectively coated on the surface of APF template after the hydrothermal conversion process [23,31]. The minor peaks at about 2922 cm−1 are associated with the stretching vibrations of methylene (eCH2) that is caused by the residual of the CTAB surfactant. The FT-IR spectrum (Fig. 2c) of the calcined sample presents the characteristic bands of phosphate (PO43−) groups. Furthermore, the absorption bands of APF resin and CTAB surfactant nearly disappear, indicating that the template and organic additive have been effectively removed during the annealing process. The FT-IR result coincides well with the XRD and EDX analysis. The morphologies of the APF resin template, [email protected](OH)CO3, and [email protected] precursors are shown in Fig. 3. The SEM and TEM images (Fig. 3a,b) show that the APF resin template consists of nearly monodisperse spheres with a narrow size distribution and smooth surfaces. The diameter of the spheres is about 370 nm. As shown in the TEM image, the spheres exhibit a black pattern, indicating that they are solid structures. Fig. 3c,d show the SEM images of [email protected](OH)CO3 precursor obtained after an urea-based homogeneous precipitation process. The as-obtained [email protected](OH)CO3 precursor inherits the spherical morphology and mono-dispersibility of the APF resin cores (Fig. 3c,d). Attributing to the coating of amorphous Gd(OH)CO3 shell on the surfaces of the APF template, a rough surface and larger sphere size (increase to 390 nm) are generated for the [email protected](OH)CO3 precursor. After the hydrothermal process, the as-synthesized sample is composed of high yield uniform urchin-like hierarchical architectures (Fig. 3e,f). The enlarged image shows that the hierarchical urchin-like spheres ([email protected]) consist of aggregates of numerous primary nanorods with tens of nanometers in length. These nanorods are closely knitted with each other to form hierarchical spheres. The result indicates that the amorphous Gd(OH)CO3 shell converts to GdPO4 nanorods during the hydrothermal process. To understand the detailed formation process of the [email protected] structure, the hydrothermal time-dependent experiments were carried out to monitor the morphology transformation (Fig. 4). When the hydrothermal time is fixed at 1 h, the Gd(OH)CO3 precursor is attacked by NH4H2PO4 and thus converts to the GdPO4 short nanorods on the surface of the APF template (Fig. 4a). By prolonging the reaction time, the Gd(OH)CO3 continues to react with NH4H2PO4 and generates more GdPO4 nanorods on the surface of template. Moreover, the nanorods grow longer and become more compact with increase of hydrothermal time (Fig. 4b–d). After 12 h, the nanorods are closely knitted with each other to form the urchin-like hierarchical architectures (Fig. 3e,f). Fig. 5 shows the SEM and TEM images of the GdPO4 sample after annealing at 500 °C for 2 h. The SEM images show that the as-obtained GdPO4 sample consists of a large scale of urchin-like hierarchical architectures (Fig. 5a,b), which inherits the morphology of the [email protected] precursor (Fig. 3e,f). A small number of ruptured spheres reveal the hollow interior of the sample, and the rupture of the hierarchical spheres are caused by the release of gaseous carbon/nitrogen oxides with the combustion during the annealing process. Moreover, the average diameters of the GdPO4 hierarchical hollow spheres obviously decrease compared with the [email protected] precursor. The size shrinkage is due to the dehydration of the cross-linked APF template and shrinkage of the as-formed GdPO4 nanorods during the annealing process. TEM image was also carried out to further explore the GdPO4 hollow structure. The strong contrast between the dark edge and the pale center provides direct evidence of the hollow structure of the hierarchical spheres (Fig. 5c). One can also observe that the shell of the hollow hierarchical spheres is constructed by a large number of nanorods, which coincides well with the SEM images (Fig. 5a,b). As disclosed by the corresponding HRTEM image from one single nanorod, the interplanar distance between the adjacent lattice fringes is determined to be 0.279 nm (Fig. 5d), which can be well indexed as the d-

Fig. 1. XRD patterns of (a) [email protected](OH)CO3 precursor, (b) hydrothermal product [email protected], and (c) GdPO4 hollow spheres. The standard data for hexagonal phase GdPO4 (JCPDS No. 39-0232) is presented as a reference. (d) EDX spectrum of the calcined GdPO4 sample.

Fig. 2. FT-IR spectra of (a) APF template, (b) hydrothermal product [email protected], and (c) calcined GdPO4 sample.

deformation vibrations and the band at 1201 cm−1 results from the AreOeC stretching. A group of bands centered at 1306, 1444, and 1508 cm−1 correspond to the CeC stretching in benzene rings, confirming the existence of aromatic ring in APF resin. Moreover, an intense band at 1620 cm−1 is due to plane NeH deformation vibration. The FT-IR result confirms the component of aminophenol-formaldehyde (APF) resin template, which agrees well with the previous literatures [32,33]. After the hydrothermal treatment, the characteristic bands of APF template almost weaken, and some new absorption bands appear (Fig. 2b). The FT-IR bands centered at 544 and 622 cm−1 are attributed to the bending vibrations of OePeO group and the band at 266

Applied Surface Science 475 (2019) 264–272

J. Tian et al.

Fig. 3. (a) SEM and (b) TEM images of APF template. SEM images of (c,d) [email protected](OH)CO3 precursor and (e,f) hydrothermal product [email protected] (180 °C, 12 h).

spacing value of the (1 0 2) plane of the GdPO4 crystal. A schematic illustration for the overall formation process of the GdPO4 hierarchical hollow spheres is illustrated in Scheme 1. Moreover, the uniform and well-dispersed APF resin microspheres with smaller particle size (280 nm) have been also synthesized according to the previous literature [32]. It can be found that the smaller GdPO4 hollow spheres can be synthesized via the similar synthesis procedure with smaller APF spheres as template (Fig. S2 in the Supplementary material). The result indicates that the GdPO4 hollow spheres with desired particle size can be obtained by simply choosing the appropriate APF resin template. The photoluminescence properties of Tb3+ and Eu3+-doped GdPO4 hollow spheres were investigated. The excitation spectrum of GdPO4:Tb3+ sample consists of an intense broad band with a maximum at 214 nm, a shoulder at 273 nm, and some weak lines between 300 and 400 nm (Fig. 6a, left). These excitation lines are assigned to the charge transfer band (CTB) between the Eu3+ and O2− ions, 8S7/2-6I11/2 transition line of Gd3+ ions, and the f-f transition lines of Tb3+ ions, respectively. The corresponding emission spectrum is composed of a group of emission lines at about 488, 542, 586, and 620 nm, which are attributed to 5D4–7FJ (J = 6, 5, 4, 3) transition lines of the Tb3+ ions (Fig. 6a, right). The characteristic green emission of Tb3+ with 5D4–7F5

transition (542 nm) is dominant in comparison with other transition lines. The emission spectrum of GdPO4:Eu3+ sample is composed of a series of emission lines centered at 588, 613, 650, and 696 nm (Fig. 6b), which can be assigned to 5D0-7FJ (J = 1, 2, 3, 4) transition lines of Eu3+ ions, respectively. The prominent emission peak at 588 nm corresponds to the 5D0–7F1 magnetic-dipole transition. It is well known that Eu3+ ions are generally utilized as probes to detect local environments for a matrix. The 5D0-7F1 transition is dominating when Eu3+ ions locate in a site with inversion symmetry while the 5D0-7F2 is the strongest transition in a site without inversion symmetry [34,37]. Thus, in this case, the Eu3+ ions locate in an inversion symmetry site in GdPO4 host matrix. We take GdPO4:Tb3+ as an example to investigate the influence of different sizes on the luminescence properties of the hollow spheres. It can be found that the GdPO4:Tb3+ samples with different particle sizes show similar spectral patterns without any emission band shift, but the smaller GdPO4:Tb3+ hollow spheres exhibit a lower photoluminescence intensity than that of the sample with bigger particle size (Fig. S3 in the Supplementary material). The photoluminescence decay curves for the Tb3+ (542 nm, 5 D4–7F5) and Eu3+ (588 nm, 5D0-7F2) ions in GdPO4 host were also investigated (Fig. 6c,d). The two decay curves can be both well fitted 267

Applied Surface Science 475 (2019) 264–272

J. Tian et al.

Fig. 4. SEM images of the hydrothermal intermediates obtained after different time intervals: (a) 1 h, (b) 2 h, (c) 4 h, (d) 8 h.

Fig. 5. (a,b) SEM, (c) TEM, and (d) HRTEM images of the GdPO4 hierarchical hollow spheres. 268

Applied Surface Science 475 (2019) 264–272

J. Tian et al.

Scheme 1. Schematic illustration for the overall formation process of the GdPO4 hierarchical hollow spheres.

Fig. 6. (a) Photoluminescence excitation and emission spectra of GdPO4:Tb3+ and (b) emission spectrum of GdPO4:Eu3+. Decay curves of the (c) GdPO4:Tb3+ and (d) GdPO4:Eu3+ samples. 269

Applied Surface Science 475 (2019) 264–272

J. Tian et al.

Fig. 7. In vitro (a) MDA-MB231 and (b) BT474 cells viabilities after incubation for 24 and 48 h with GdPO4 hollow spheres at different concentrations by MTT assay.

into a double-exponential function as I = A1 exp(-t/τ1) + A2 exp(-t/τ2), and the average lifetimes of GdPO4:Tb3+ and GdPO4:Eu3+ samples are determined to be 3.94 and 2.79 ms, respectively (Fig. 6c,d). The result is in good accordance with other Eu3+ and Tb3+ doped phosphors [18,23]. The biocompatibility of the materials is significant as a potential drug carrier for the practical applications in biomedical field. The in vitro cytotoxicity tests of the GdPO4 hierarchical hollow spheres were examined by an MTT assay with MDA-MB231 and BT474 cells (Fig. 7). As shown in Fig. 7a, those incubated with MDA-MB231 cells exhibit relatively high cell viability (> 100%) at all tested concentrations for 24 and 48 h. As can be seen from Fig. 7b, BT474 cells also display relatively high cell viability (> 90%) at all the dosages for 24 and 48 h. The above experimental results reveal that the as-synthesized GdPO4 hierarchical hollow spheres are biocompatible and may be promising to be applied in field of drug delivery. In this work, we selected Ibuprofen (IBU) as a model drug to investigate the drug loading and release properties of GdPO4 sample. The FT-IR spectra of GdPO4 hollow spheres, pure IBU, and IBU-loaded GdPO4 are illustrated in Fig. 8a–c. In Fig. 8b, the absorption band at 1718 cm−1, 2962 (2868) cm−1, 1510 (1462) cm−1, 1422 cm−1, and 1322 cm−1 are originated from eCOOH, CeHx bonds, quaternary carbon atom, eOH bending vibration, and tertiary carbon atom of the IBU molecules, which can effectively confirm the structure of IBU. For the IBU loaded GdPO4 (IBU-GdPO4) sample, the characteristic bands of IBU molecules can be detected besides the absorption bands of GdPO4 (Fig. 8c). The result reveals that IBU can be effectively loaded onto the GdPO4 hierarchical hollow spheres. The loading efficiency of drug molecules was monitored by thermogravimetric (TG) result (Fig. 8d). Compared with the TG data between the pure GdPO4 hollow spheres and IBU-GdPO4 sample, the IBU loading degree for drug delivery system is determined to be 28.46 wt%. The drug release behavior of the GdPO4 hierarchical hollow spheres was investigated by ultraviolet spectrophotometer. The IBU calibration curve is in good accordance with the Lambert and Beers law (inset in

Fig. 8. FT-IR spectra of (a) GdPO4, (b) pure IBU, and (c) IBU-GdPO4. (d) TG curves of (a) GdPO4 hollow spheres and (b) IBU-GdPO4.

Fig. 9a). The corrected released IBU concentration was calculated by the following equation:

Ccort = Capp +

V Vt

t−1

∑ Capp 0

Fig. 9a shows the cumulative drug release behavior of IBU-GdPO4 in SBF solution with the physiological pH = 7.4. The system shows an initial burst release of 40% within 12 h followed by an extremely sustained release till nearly 100% within 72 h, exhibiting an excellent sustained drug release patterns. The initial burst release may be assigned to physical adsorption of IBU on the exterior surface of GdPO4 hollow spheres, and the sustained release of IBU can be attributed to the strong interaction between GdPO4 and IBU (hydrogen bonding). In addition, we take GdPO4:Tb3+ sample as an example to investigate the influence of the cumulatively released IBU on luminescence emission intensity of IBU–GdPO4:Tb3+ system. Fig. 9b shows the emission spectra of pure GdPO4:Tb3+, IBU–GdPO4:Tb3+, and the IBU–GdPO4:Tb3+ system at different release time intervals (12 and 36 h). One can see that the emission intensity decreases dramatically when the IBU molecules are loaded into the GdPO4:Tb3+ hollow spheres, which can be assigned to the quenching effect of Tb3+ luminescence by IBU molecules with high vibrational frequencies. Moreover, the luminescence intensity gradually increases by a cumulative release of the IBU molecules. This above characteristic make the drug carrier be applied as a luminescent probe for tracking the drug release process. The result agrees well with our previous reports [38,39]. Apart from the excellent candidate for luminescent materials, the 270

Applied Surface Science 475 (2019) 264–272

J. Tian et al.

Fig. 9. (a) Cumulative IBU release profile of IBU loaded GdPO4 system in SBF as a function of release time. Inset is the corresponding calibration curve. (b) Luminescence emission spectra of pure GdPO4:Tb3+ and IBU-GdPO4:Tb3+ at different release time intervals. Fig. 10. (a) Magnetization plots of the GdPO4 hierarchical hollow spheres as a function of the applied fields at 300 K. (b) T1-weighted images for various Gd concentrations (0–3 mM) of GdPO4 hierarchical hollow spheres. Deionized water (0 mM) was used as the reference. (c) T1 relaxivity plot of aqueous suspension of GdPO4 sample.

as-obtained GdPO4 hierarchical hollow spheres exhibit attractive paramagnetic properties [40]. The magnetization behavior of GdPO4 sample as a function of applied field ranging from −20 to 20 kOe at 300 K is shown in Fig. 10a. The result indicates that the GdPO4 sample exhibits paramagnetic properties. The paramagnetic behavior is primarily assigned to the unpaired 4f electrons of Gd3+ ions, which are closely bound to the nucleus and shielded by the outer closed shell electrons from the crystal field [41,42]. The magnetization and magnetic mass susceptibility of the GdPO4 hierarchical hollow spheres are determined to be ∼1.71 emu/g at 20kOe and ∼8.60 × 10−5 emu/gOe, which may find potential application in field of magnetic resonance imaging (MRI) [29,43]. The as-obtained GdPO4 hierarchical hollow spheres were evaluated for the T1-weighted images and relaxivity. Fig. 10b shows the T1-weighted MR images of the GdPO4 sample at different Gd3+ concentrations. It can be seen that the T1-weighted MR imaging signal intensity increases evidenced by the brighter images by increasing the Gd3+ concentration (Fig. 10b). Furthermore, the relaxivity parameters (r1) of a series of GdPO4 hollow spheres with different molar concentrations of Gd3+ have been investigated according to the slope of the concentration-dependent relaxation rate 1/T1 graphs. A good linear relationship can be obtained when Gd3+ concentration is plotted against 1/T1 (Fig. 10c). The specific relaxivity value r1 is determined to be 1.171 mM−1 s−1, indicating that the as-synthesized GdPO4 composites may find potential applications as a T1 contrast agent for MRI.

4. Conclusion In summary, a novel template-directed synthesis strategy has been developed to synthesize well-defined GdPO4 hierarchical hollow spheres. The tunable particle sizes of the hollow spheres may be realized by simply adjusting the particle size of the phenol formaldehyde resin template. The crystal structure, morphology, luminescent and magnetic properties, and biocompatibility of the as-obtained GdPO4 hierarchical hollow spheres were characterized by XRD, FT-IR, EDX, SEM, TEM, PL, kinetic decay, magnetization plots, MRI, and MTT assay, respectively. The GdPO4 sample exhibits well-defined urchin-like hollow spherical structure, good biocompatibility, attractive paramagnetic nature, and positive signal-enhancement ability. The drug delivery system reveals high drug loading capacity and sustained release patterns. After doping Eu3+ and Tb3+ into the GdPO4 host, the samples exhibit light emissions with different colors corresponding to the characteristic transitions of the activator ions, which can be applied to track and monitor the drug release process based on the change in luminescence intensity. Hence the as-synthesized materials can serve as a multifunctional platform for applications of bioimaging and drug delivery. 271

Applied Surface Science 475 (2019) 264–272

J. Tian et al.

Conflicts of interest [20]

There are no conflicts of interest to declare.

[21]

Acknowledgements This research was supported by the National Natural Science Foundations of China (21301046, 51302062), Natural Science Foundation of Hebei Province (B2017201125, B2017201100), the Second Batch of Top Youth Talent Support Program of Hebei Province, Distinguished Young Scholars Fund of Hebei University (2015JQ04), Research Plans of the Natural Science Foundations (2012-234), and Laboratory Open Foundations of Hebei University (sy201830).

[22]

[23]

[24]

Appendix A. Supplementary material

[25]

Supplementary data to this article can be found online at https:// doi.org/10.1016/j.apsusc.2018.12.262.

[26]

References [27] [1] X. Wang, J. Feng, Y. Bai, Q. Zhang, Y. Yin, Synthesis, properties, and applications of hollow micro-/nanostructures, Chem. Rev. 116 (2016) 10983–11060. [2] X.W. Lou, L.A. Archer, Z. Yang, Hollow micro-/nanostructures: synthesis and applications, Adv. Mater. 20 (2010) 3987–4019. [3] H.J. Fan, U. Gösele, M. Zacharias, Formation of nanotubes and hollow nanoparticles based on kirkendall and diffusion processes: a review, Small 3 (2007) 1660–1671. [4] F. Zhang, Y. Shi, X. Sun, D. Zhao, G.D. Stucky, Formation of hollow upconversion rare-earth fluoride nanospheres: nanoscale kirkendall effect during ion exchange, Chem. Mater. 21 (2009) 5237–5243. [5] X. Yu, D. Wang, Q. Peng, Y. Li, High performance electrocatalyst: Pt–Cu hollow nanocrystals, Chem. Commun. 47 (2011) 8094–8096. [6] H.J. Kim, K.I. Choi, A. Pan, I.D. Kim, H.R. Kim, K.M. Kim, C.M. Na, G. Cao, J.H. Lee, Template-free solvothermal synthesis of hollow hematite spheres and their applications in gas sensors and Li-ion batteries, J. Mater. Chem. 21 (2011) 6549–6555. [7] S. Gai, C. Li, P. Yang, J. Lin, Recent progress in rare earth micro/nanocrystals: soft chemical synthesis, luminescent properties, and biomedical applications, Chem. Rev. 114 (2014) 2343–2389. [8] K. Ge, C. Zhang, W. Sun, H. Liu, Y. Jin, Z. Li, X.J. Liang, G. Jia, J. Zhang, Upconversion Y2O3:Yb3+, Er3+ hollow spherical drug carrier with improved degradability for cancer treatment, ACS Appl. Mater. Interfaces 8 (2016) 25078–25086. [9] Y. Zeng, X. Wang, H. Wang, Y. Dong, Y. Ma, J.N. Yao, Multi-shelled titania hollow spheres fabricated by a hard template strategy: enhanced photocatalytic activity, Chem. Commun. 46 (2010) 4312–4314. [10] Y.Q. Wang, G.Z. Wang, H.Q. Wang, C.H. Liang, W.P. Cai, L.D. Zhang, Chemicatemplate synthesis of micro/nanoscale magnesium silicate hollow spheres for waste-water treatment, Chem. Eur. J 16 (2010) 3497–3503. [11] L. Zhang, G. Jia, H. You, K. Liu, M. Yang, Y. Song, Y. Zheng, Y. Huang, N. Guo, H. You, Sacrificial template method for fabrication of submicrometer-sized YPO4:Eu3+ hierarchical hollow spheres, Inorg. Chem. 49 (2010) 3305–3309. [12] G. Jia, H. You, Y. Song, Y. Huang, M. Yang, H. Zhang, Facile synthesis and luminescence of uniform Y2O3 hollow spheres by sacrificial template route, Inorg. Chem. 49 (2010) 7721–7725. [13] G. Jia, H. You, K. Liu, Y. Zheng, N. Guo, H. Zhang, Highly uniform Gd2O3 hollow microspheres: template-directed synthesis and luminescence properties, Langmuir 26 (2010) 5122–5128. [14] Z. Hou, Y. Zhang, K. Deng, Y. Chen, X. Li, X. Deng, Z. Cheng, H. Lian, C. Li, J. Lin, UV-emitting upconversion-based TiO2 photosensitizing nanoplatform: NearInfrared light mediated in vivo photodynamic therapy via mitochondria-involved apoptosis pathway, ACS Nano 9 (2015) 2584–2599. [15] D. Wang, B. Liu, Z. Quan, C. Li, Z. Hou, B. Xing, J. Lin, New advances on the marrying of UCNPs and photothermal agents for imaging-guided diagnosis and the therapy of tumors, J. Mater. Chem. B 5 (2017) 2209–2230. [16] A. Louie, Multimodality imaging probes: design and challenges, Chem. Rev. 110 (2010) 3146–3195. [17] J. Zhou, Y. Sun, X. Du, L. Xiong, H. Hu, F.Y. Li, 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 31 (2010) 3287–3295. [18] T. Grzyb, A. Gruszeczka, R.J. Wiglusz, Z. Sniadecki, B. Idzikowski, S. Lis, Multifunctionality of GdPO4:Yb3+, Tb3+ nanocrystals–luminescence and magnetic behavior, J. Mater. Chem. 22 (2012) 22989–22997. [19] W. Ren, G. Tian, L. Zhou, W. Yin, L. Yan, S. Jin, Y. Zu, S. Li, Z. Gu, Y. Zhao,

[28]

[29]

[30]

[31]

[32]

[33]

[34]

[35] [36]

[37]

[38]

[39]

[40]

[41]

[42]

[43]

272

Lanthanide ion-doped GdPO4 nanorods with dual-modal bio-optical and magnetic resonance imaging properties, Nanoscale 4 (2012) 3754–3760. N. Babayevska, P. Florczak, M. Woźniak-Budych, M. Jarek, G. Nowaczyk, T. Zalewski, S. Jurga, Functionalized multimodal [email protected] nanosystems to use as perspective contrast agent for MRI, App. Surface Sci. 404 (2017) 129–137. J.M. Kinsella, S. Ananda, J.S. Andrew, J.F. Grondek, M.P. Chien, M. Scadeng, N.C. Gianneschi, E. Ruoslahti, M.J. Sailor, Enhanced magnetic resonance contrast of Fe3O4 nanoparticles trapped in a porous silicon nanoparticle host, Adv. Mater. 23 (2011) H248–H253. T. Zhou, B.Y. Wu, D. Xing, Bio-modified Fe3O4 core/Au shell nanoparticles for targeting and multimodal imaging of cancer cells, J. Mater. Chem. 22 (2012) 470–477. S. Rodriguez-Liviano, A.I. Becerro, D. Alcántara, V. Grazú, J.M. de la Fuente, M. Ocaña, Synthesis and properties of multifunctional tetragonal Eu:GdPO4 nanocubes for optical and magnetic resonance imaging applications, Inorg. Chem. 52 (2013) 647–654. L.M. Manus, D.J. Mastarone, E.A. Waters, X.Q. Zhang, E.A. Schultz-Sikma, K.W. MacRenaris, K.W. MacRenaris, D. Ho, T.J. Meade, Gd(III)-nanodiamond conjugates for MRI contrast enhancement, Nano Lett. 10 (2010) 484–489. C.C. Huang, C.H. Su, W.M. Li, T.Y. Liu, J.H. Chen, C.S. Yeh, Bifunctional Gd2O3/C nanoshells for MR Imaging and NIR therapeutic applications, Adv. Funct. Mater. 19 (2009) 249–258. K. Deng, Z. Hou, X. Deng, P. Yang, C. Li, J. Lin, Enhanced antitumor efficacy by 808 nm laser-induced synergistic photothermal and photodynamic therapy based on a indocyanine-Green-Attached W18O49 nanostructure, Adv. Funct. Mater. 25 (2015) 7280–7290. Y. Fan, Z. Hu, J. Yang, C. Zhang, L. Zhu, Ultrasonic-assisted synthesis of core–shell structure CePO4:Tb/GdPO4 and GdPO4/CePO4: Tb nanophosphors and their photoluminescence properties, App. Surface Sci. 266 (2013) 22–26. J.C. Zhou, L.D. Sun, J. Shen, J.Q. Gu, C.H. Yan, Fluorescent-magnetic nanocrystals: synthesis and property of YPxV1-xO4:[email protected] core/shell structure, Nanoscale 3 (2011) 1977–1983. Q. Du, Z. Huang, Z. Wu, X. Meng, G. Yin, F. Gao, L. Wang, Facile preparation and bifunctional imaging of Eu-doped GdPO4 nanorods with MRI and cellular luminescence, Dalton Trans. 44 (2015) 3934–3940. A.I. Becerro, S. Rodríguez-Liviano, A.J. Fernández-Carrión, M. Ocaña, A novel 3D architecture of GdPO4 nanophosphors: multicolored and white light emission, Cryst. Growth Des. 13 (2013) 526–535. L. Zhang, M. Yin, H. You, M. Yang, Y. Song, Y. Huang, Mutifuntional GdPO4:Eu3+ hollow spheres: synthesis and magnetic and luminescent properties, Inorg. Chem. 50 (2011) 10608–10613. J. Zhao, W. Niu, L. Zhang, H. Cai, M. Han, Y. Yuan, S. Majeed, S. Anjum, G. Xu, A template-free and surfactant-free method for high-yield synthesis of highly monodisperse 3-aminophenol−formaldehyde resin and carbon nano/microspheres, Macromolecules 46 (2013) 140–145. J. Zhao, R. Luque, W. Qi, J. Lai, W. Gao, M.R.H.S. Gilani, G. Xu, Facile surfactantfree synthesis and characterization of [email protected] coreshell magnetic microspheres, J. Mater. Chem. A 3 (2015) 519–524. C. Zhang, W. Wei, J. Zhang, Y. Li, G. Zhou, G. Jia, Uniform mesoporous CaSiO3:Eu3+ nanospheres: template-directed synthesis, luminescence and sustained drug release properties, Dyes Pigments 136 (2017) 427–433. M. Bohnera, J. Lemaitre, Can bioactivity be tested in vitro with SBF solution? Biomaterials 30 (2009) 2175–2179. J.G. Li, X.D. Li, X.D. Sun, T. Ikegami, T. Ishigaki, Uniform colloidal spheres for (Y1xGdx)2O3: formation mechanism, compositional impacts, and physicochemical properties of the oxides, Chem. Mater. 20 (2008) 2274–2281. C. Li, J. Yang, P. Yang, H. Lian, J. Lin, Hydrothermal synthesis of lanthanide fluorides LnF3 (Ln = La-Lu) nano/microcrystals with multiform structures and morphologies, Chem. Mater. 20 (2008) 4317–4326. C. Zhang, C. Li, S. Huang, Z. Hou, Z. Cheng, P. Yang, C. Peng, J. Lin, Self-activated luminescent and mesoporous strontium hydroxyapatite nanorods for drug delivery, Biomaterials 31 (2010) 3374–3383. C. Zhang, C. Li, C. Peng, R. Chai, S. Huang, D. Yang, Z. Cheng, J. Lin, Facile and controllable synthesis of monodisperse CaF2 and CaF2:Ce3+/Tb3+ hollow spheres as efficient luminescent materials and smart drug carriers, Chem. Eur. J. 16 (2010) 5672–5680. S. Viswanathan, Z. Kovacs, K.N. Green, S.J. Ratnakar, A.D. Sherry, Alternatives to gadolinium-based metal chelates for magnetic resonance imaging, Chem. Rev. 110 (2010) 2960–3018. S.J. Zeng, M.K. Tsang, C.F. Chan, K.L. Wong, J.H. Hao, PEG modified BaGdF5:Yb/Er nanoprobes for multi-modal upconversion fluorescent, in vivo X-ray computed tomography and biomagnetic imaging, Biomaterials 33 (2012) 9232–9238. S.J. Zeng, H.B. Wang, W. Lu, Z.G. Yi, L. Rao, H.R. Liu, J. Hao, Dual-modal upconversion fluorescent/X-ray imaging using ligand-free hexagonal phase NaLuF4:Gd/Yb/Er nanorods for blood vessel visualization, Biomaterials 35 (2014) 2934–2941. X. Kang, D. Yang, Y. Dai, M. Shang, Z. Cheng, X. Zhang, H. Lian, P. Ma, J. Lin, Poly (acrylic acid) modified lanthanide-doped GdVO4 hollow spheres for up-conversion cell imaging, MRI and pH-dependent drug release, Nanoscale 5 (2013) 253–261.