Article Cite This: Chem. Mater. 2017, 29, 10455−10468
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Controllable Synthesis of Manganese Oxide Nanostructures from 0‑D to 3‑D and Mechanistic Investigation of Internal Relation between Structure and T1 Relaxivity Zhenghuan Zhao,*,† Jianfeng Bao,‡ Chen Fu,† Ming Lei,† and Jingliang Cheng§ †
College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China College of Medical Technology and Engineering, Henan University of Science and Technology, Luoyang 471000, China § Department of Radiology, First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China ‡
S Supporting Information *
ABSTRACT: Since manganese oxide nanomaterials attract wide attention in the biomedical and energy fields, understanding the inner relationship between their properties and structures is fundamental and urgently needed. However, controllable synthesis of metal oxide nanomaterials with diverse morphologies is still a persistent challenge. Herein, various anisotropic manganese oxide nanostructures from zero-dimensional (0-D) to three-dimensional (3-D) were successfully fabricated through thermal decomposition. We observed that chloride ions can assist the formation of 0-D nanooctaherals, nanocubes, and nanooctapods due to its binding capacity to the manganese ions on the nanocrystal surface. Interestingly, the procedural heating process can affect the decomposition rate of the manganese−oleate, which drives a substantial reduction in the surface free energy by sharing a common crystallographic orientation and leads to the formation of 1-D and 3-D nanostructures by oriented attachment growth. On the basis of systematic analyses, surface-to-volume ratio, surface manganese ion density, and geometrical confinement determined by specific morphology are found to be the key parameters to achieve high-performance T1 relaxivity. Moreover, the screened out manganese oxide nanocubes with high r1 value exhibit good contrast ability in T1-weighted MRI imaging in vitro and in vivo, showing a great potential for lesion detection in T1 contrast imaging. This study builds a link between controllable synthesis of manganese oxide nanomaterials and its property and, thus, provides a rational design clue to develop highperformance magnetic oxide nanomaterials, especially in the biomedical and energy fields.
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INTRODUCTION Due to the wide application in biomedical applications, catalysis, energy and data storage devices, and chemical analysis, developing a new magnetic oxide nanostructure with unique features and high performance is of great importance for both fundamental science and technical applications.1−7 Among various magnetic oxide nanomaterials (e.g., iron oxide, manganese oxide, and gadolinium oxide), manganese oxide (MO) nanomaterials with unique physical properties have recently received extensive attention,8,9 especially as contrast agents for shortening of the spin−lattice (or longitudinal) relaxation time, T1.10,11 Compared to the traditional superparamagnetic iron oxide nanoparticles (e.g., magnetite), utilizing MO nanomaterials as contrast agents can avoid the misleading diagnosis caused by the confusion between lesion and signals from bleeding, calcification, or metal deposits.12 Unfortunately, suffering from its relatively low T1 relaxivity, high dosage MO nanoparticles are acquired to assess lesion detection. This disadvantage increases the potential risk of adverse effects and limits the application of MO nanoparticles in clinical diagnoses.13 On the basis of the Solomon, © 2017 American Chemical Society
Bloembergen, and Morgan (SBM) theory, T1 contrast ability is highly dependent on the chemical exchange efficiency between magnetic ions and proton.14,15 It has been recently noticed that controlling the morphology of magnetic oxide nanocrystals or forming three-dimensional (3-D) magnetic oxide nanoclusters has been shown theoretically and experimentally to improve T1 or T2 relaxivity.16−18 Therefore, systematic synthesis of a series of MO nanoparticles with various structures to figure out the inner relationship between the structure of the MO nanoparticles and their T1 contrast property is urgent and can accelerate the development of highperformance manganese oxide based T1 contrast agent. In general, the precise control of the morphology of zerodimensional (0-D) nanostructures are based on tuning the different growth rate in a specific direction in the crystal growth process. The most common way to fabricate the anisotropic nanomaterials with various morphologies is introduction a Received: September 27, 2017 Revised: December 4, 2017 Published: December 4, 2017 10455
DOI: 10.1021/acs.chemmater.7b04100 Chem. Mater. 2017, 29, 10455−10468
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Chemistry of Materials selective capping agent.19−22 The presence of a capping agent can change the order of free energies for different crystallographic planes, and thus their relative growth rates, and form the anisotropic nanoparticles. Whereas, synthesis of complicated nanostructure in high dimensions is controlled by the aggregation-based crystal growth. By slowing down the growth of the nuclei, the nearby nanoseeds may share a common crystallographic to elimination high energy surface and form the complicated nanostructures by oriented attachment and secondary growth.23−27 In the past decades, some strategies have been used to successfully synthesize monodisperse metal nanocrystructures (e.g., Au, Pt, Pd, and their alloys) with a variety of anisotropic morphologies, including rod, spheroid, cube, octahedron, octahedron, and octapods.28−32 Unfortunately, it is still a huge challenge to precisely control the morphology of MO nanomaterials from 0-D to 3-D due to their diverse crystal packing structure, strong metal−oxygen covalent bonding, and variable oxidation states.33,34 In the past few years, thermal decomposition of metal (e,g, Fe, Mn, and Gd) precursor in high-boiling-point solvents have been developed to produce magnetic oxide nanoparticles with high crystallinity, narrow size distribution (σ ≤ 5%), and large scale.35−40 Recent progress showed that anisotropic magnetic oxide nanoparticles could form by controlling the reaction temperature, selecting the proper surfactant, and introducing proper selective capping agents.16,41−43 However, synthesis of various MO nanostructures from 0-D to 3-D and explore their formation mechanism is rare. In this study, we report a morphology controllable synthesis of MO nanostructures by thermal decomposition of the Mn−oleate complex through procedural heating process and chloride assisted growth. We observed that the heating rate and chloride ion can effectively affect the morphology of the final product. Various 0-D MO nanostructures with the morphologies of cubes, octapods, and octahedral were successfully synthesized. Additionally, we obtained not only 1-D rod-shaped MO nanostructures but also self-assembled nanocluster and nanowhisker MO nanostructures in 3-D by oriented attachment. More importantly, this work provided adequate sources to explore the internal relation between the morphology and T1 relaxation time, shortening effects in MRI. The obtained MO nanostructures with high surface-to-volume ratio, surface manganese ion density, and geometrical confinement can exhibit strong T1 contrast capacity. Additionally, further cell and animal study shows that the screened out MO nanocubes with highest r1 values are suitable as high-performance T1 contrast agents for in vivo MRI. These results may provide clues to developing highperformance nanomaterials, especially metal oxide nanomaterials, based on the morphology−capacity relationship in biomedical and energy application.
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mass spectroscopy (ICP-MS). M−H curves were obtained by on a Quantum Design MPMS-XL-7 system. The MRI testing and T1 relaxation time measurements were tested at a 0.5 T NMR120Analyst NMR Analyzing & Imaging system (Niumag Corporation, Shanghai, China). In vivo MR images measurements were performed on a 7 T MRI scanner (Varian 7 T micro MRI System). Synthesis of 0-D Truncated MO Nanooctahedrons (MOOHs). In a typical experiment, 0.6 g of Mn−oleate (0.97 mmol), 155 μL of oleic acid, and 20 mg of sodium chloride were dissolved in 12 mL of 1octadecene at room temperature. The mixture was degassed in vacuum for 30 min and backfilled with argon to remove any low volatile impurities and oxygen at room temperature. And then, we heated the reaction solution to 320 °C rapidly and maintained this mixture at that temperature for 1 h. The resultant solution was then cooled to room temperature and mixed with 30 mL of isopropanol to precipitate the nanoparticles. The nanoparticles were separated by centrifugation and washed three times with ethanol. After washing, the nanoparticles were dissolved in hexane for long-term storage at 4 °C. Synthesis of 0-D MO Nanocubes (MOCs). In a typical experiment, 0.6 g of Mn−oleate (0.97 mmol), 155 μL of oleic acid, and 20 mg of sodium chloride were dissolved in 12 mL of 1octadecene at room temperature. The mixture was degassed in vacuum for 30 min and backfilled with argon to remove any low volatile impurities and oxygen at room temperature. And then, we heated the reaction solution to 200 °C with a constant heating rate of 3.3 °C min−1 and remained at that temperature for 20 min. After cooling this mixture to room temperature, we heated it to 320 °C rapidly and maintained this mixture at that temperature for 40 min. The resultant solution was then cooled to room temperature and mixed with 30 mL isopropanol to precipitate the nanoparticles. The nanoparticles were separated by centrifugation and washed three times with ethanol. After washing, the nanoparticles were dissolved in hexane for long-term storage at 4 °C. Synthesis of 0-D MO Nanooctapods (MOOPs). The procedure of synthesis of MOOPs is similar to that of MOCs. After heating to 320 °C, the solution was kept at that temperature for 150 min. The nanoparticles were separated by centrifugation and washed three times with ethanol. After washing, the nanoparticles were dissolved in hexane for long-term storage at 4 °C. Synthesis of 1-D MO Nanorods (MORs). In a typical experiment, 0.8 g of Mn−oleate (1.30 mmol) and 206 μL of oleic acid were dissolved in 12 mL of 1-octadecene at room temperature. The mixture was degassed in vacuum for 30 min and backfilled with argon to remove any low volatile impurities and oxygen at room temperature. And then, we heated the reaction solution to 200 °C with a constant heating rate of 3.3 °C min−1 and remained at temperature for 20 min. After cooling this mixture to room temperature, we heated it to 320 °C rapidly and maintained this mixture at that temperature for 1 h. The resultant solution was then cooled to room temperature and mixed with 30 mL of isopropanol to precipitate the nanoparticles. The nanoparticles were separated by centrifugation and washed three times with ethanol. After washing, the nanoparticles were dissolved in hexane for long-term storage at 4 °C. Formation of 2-D Manganese Oxide Superlattice. The formation of the 2-D superlattice manganese oxide superlattice was carried out as follows. Typically, 0.1 mL of manganese oxide nanospheres dispersed in hexane was gently deposited on the copper grid. The copper grid was placed in the fume hood to slowly evaporate hexane overnight. After the hexane was removed completely under vacuum, the 2-D manganese oxide superlattice was obtained. Synthesis of 3-D Branched MO Nanoassembled Structure (BMOAs). In a typical experiment, 0.6 g of Mn−oleate (0.97 mmol), 155 μL oleic acid, and 18 mg of sodium chloride were dissolved in 10 mL of phenyl ether at room temperature. The mixture was degassed in vacuum for 30 min and backfilled with argon to remove any low volatile impurities and oxygen at room temperature. And then, we heated the reaction solution to 210 °C with a constant heating rate of 2 °C min−1, and it remained at that temperature for 20 min. After cooling this mixture to room temperature, we heated it to 260 °C rapidly and maintained this mixture at that temperature for 1 h. The
EXPERIMENTAL SECTION
Reagent. Oleic acid (tech 90%), manganese(II) chloride tetrahydrate (tech 90%), phenyl ether (99%), and 1-octadecene (90%) were purchased from Alfa Aesar. NaCl (AR), sodium hydroxide, hexane, tetrahydrofuran, dopamine hydrochloride, sodium oleate, isopropanol, and ethanol were purchased from Sinopharm Chemical Reagent Co. Ltd. (Shanghai, China). All chemicals were used as received without further purification. Characterizations. Transmission electron microscopy (TEM) images were captured on a JEM-2100 microscope at an accelerating voltage of 200 kV. The X-ray diffraction (XRD) patterns were obtained X-ray powder diffraction (PANalytical X’Pert3 Powder). The element analysis of Mn was determined by inductively coupled plasma 10456
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Figure 1. Controlled synthesis of 0-D and 1-D anisotropic MO nanostructures. TEM images of monodispersed (a) MOOHs, (d, e) MORs, (g) MOCs, and (i) MOOPs, respectively. Insets show the geometric model. The side lengths of MOOHs, MOCs, and MOOPs are 22.44, 9.33, and 25.87 nm. The size of MORs is 284.22 nm in length and 19.61 nm in width. HRTEM images of (b, c) MOOHs, (f) MORs, (h) MOCs, and (j) MOOPs, respectively. Insets show the geometric model. These results suggest that MOOHs and MOCs are composed by {111} and {100} basal facets. The MORs reveal uniform lattice fringes in an independent area, which may be ascribed to the oriented attachment growth. resultant solution was then cooled to room temperature and mixed with 30 mL of isopropanol to precipitate the nanoparticles. The nanoparticles were separated by centrifugation and washed three times with ethanol. After washing, the nanoparticles were dissolved in hexane for long-term storage at 4 °C. Synthesis of 3-D Spherical MO Nanoassembled Structures (SMOAs). In a typical experiment, 0.6 g of Mn−oleate (0.97 mmol), 155 μL of oleic acid, and 10 mg of sodium chloride were dissolved in 10 mL of phenyl ether at room temperature. The mixture was degassed in vacuum for 30 min and backfilled with argon to remove any low volatile impurities and oxygen at room temperature. Then, we heated the reaction solution to 210 °C with a constant heating rate of 2 °C min−1, and kept it at that temperature for 20 min. After cooling this mixture to room temperature, we heated it to 260 °C rapidly and maintained this mixture at that temperature for 1 h. The resultant solution was then cooled to room temperature and mixed with 30 mL of isopropanol to precipitate the nanoparticles. The nanoparticles were separated by centrifugation and washed three times with ethanol. After washing, the nanoparticles were dissolved in hexane for long-term storage at 4 °C. Synthesis of 3-D MO Nanowhiskers (MOWs). In a typical experiment, 0.6 g of Mn−oleate (0.97 mmol) and 155 μL of oleic acid were dissolved in 10 mL of phenyl ether at room temperature. The mixture was degassed in vacuum for 30 min and backfilled with argon to remove any low volatile impurities and oxygen at room temperature. And then, we heated the reaction solution to 210 °C with a constant heating rate of 2 °C min−1, and kept it at that temperature for 20 min. After cooling this mixture to room temperature, we heated it to 260 °C
rapidly and maintained this mixture at that temperature for 40 min. The resultant solution was then cooled to room temperature and mixed with 30 mL of isopropanol to precipitate the nanoparticles. The nanoparticles were separated by centrifugation and washed three times with ethanol. After washing, the nanoparticles were dissolved in hexane for long-term storage at 4 °C. In Vitro MRI Imaging. We incubated 1 × 107 HepG2 cells with MOCs at 37 °C for 0.25, 1.5, and 3 h in the culture media with the pH value of 7.4. The cells were harvested and washed with PBS buffer three times to remove the free MOCs. Then we concentrated the cells at the button of EP tube by centrifugation and performed T1-weighted MRI imaging on a 0.5 T NMI20-Analyst NMR system. The samples were scanned using a multiecho T1-weighted fast spin echo imaging sequence (TR/TE = 100/12 ms, 256 matrices, thickness = 1 mm, NS = 16). In Vivo Liver MR Imaging. Animal experiments were executed according to the protocol approved by Institutional Animal Care and Use Committee of Southwest University. We chose BALB/c mouse (6 weeks old, 18−22 g) as the model. After intravenously injecting MOCs or MOSs-9 into the mice (2 mg Mn/kg of mouse body weight each), the coronal and transverse plane MR images were scanned using a sequence (TR/TE = 400/10 ms, 256 × 256 matrices, thickness = 1 mm, FOV = 50 × 50) on a Varian 7 T microMRI scanner. The MR images were obtained at pre-injection and 1 h post-injection (n = 3/ group). To qualify the signal enhancement, we calculated the signal-tonoise ratio (SNR) by the equation: SNRliver = SIliver/SDnoise, where SI represents signal intensity and SD represents standard deviation. 10457
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RESULTS AND DISCUSSION Synthesis and Characterization of MO Nanostructure from 0-D to 2-D. We synthesized MO nanostructures by thermal decomposition of Mn−oleate in 1-octadecene (ODE) solvent. Due to the isotropic growth of crystal facet dominating, MO nanospheres (MOSs) were formed without any other treatment. The diameter of the MOSs can be tuned by extending the reaction time in a reproducible way (Supporting Information, Figure S1). Interestingly, solvent evaporation from colloidal dispersions results in the MOSs aligning quite regularly to form a highly ordered 2-D superlattice structure, which could be ascribed to the extremely narrow size distribution (Supporting Information, Figure S2).44 To obtain the anisotropic MO nanostructures, we introduce chloride ions to bind to the surface manganese ion to reduce the order of free energies of crystallographic planes. Additionally, a procedural heating process was utilized to control the decomposition rate of Mn−oleate, which can effectively affect the formation rate of the nucleus, saturation level of the growth materials, and reaction equilibrium. By only introducing a trace amount of chloride ions into this system, we obtained uniform truncated MO nanooctahedrons (MOOHs). The transmission electron microscopy (TEM) images show that the as-prepared products have uniform truncated octahedron morphology with high yield (>95%). The edge lengths of these MOOHs are appropriate, 22.44 ± 1.43 nm (Figure 1a and Supporting Information, Figure S3). To better visualize the three-dimensional structure of this nanostructure, we analyzed it along the [110] and [111] zone axis by high-resolution TEM (HRTEM). We noticed that the interplanar spacing distances are 2.58 and 1.58 Å, which could be assigned to the (111) and (220) plane of manganese oxide, respectively (Figure 1b,c). These results suggest that the truncated MOOHs are mainly exposed by eight {111} facets, which are polar facets composed of Mn cations and exhibit much higher energy density than the nonpolar facet.45 Additionally, we synthesized MO nanostructures with a procedural heating process without adding chloride ions. Interestingly, elongated rod-shaped and cross-shaped MO nanostructures were generated. TEM images indicate that the aspect ratio of these MO nanorods (MORs) is approximately 14 (with the length of 284.22 ± 11.91 nm and width of 19.61 ± 1.47 nm), which is located in the typical range of nanorods (Figure 1d,e and Supporting Information, Figure S3).46,47 Also, the widths of the branches of the cross-shaped ones are the same, suggesting that they grow out from a central core. After carefully surveying these unique nanoparticles, we found that the edges of these nanorods are not smooth. The HRTEM image reveal the uniform lattice fringes with the length of 2.24 Å, which is the (200) plane of manganese oxide, in the independent area (Figure 1f). This unusual phenomenon may imply the anisotropic growth of MO nanostructure proceeded by the oriented attachment mechanism. It is interesting that when we introduced chloride and the procedural heating process simultaneously in the system, we obtained the MO nanostructure with cubic morphology. TEM images show that all as-prepared MO nanocubes (MOCs) are nearly cubic morphologies with the side length of 9.33 ± 0.68 nm in high yield (Figure 1g and Supporting Information, Figure S3). Along the [100] zone axis, HRTEM images reveal that all MOCs possess the same interplanar distance of about 1.58 Å, which could be assigned to the (220) plane of manganese oxide (Figure 1h). These results suggest that all obtained MOCs are
composed of six {100} basal facets. Fascinatingly, we made MO nanooctapods (MOOPs) by only extending the reaction time to form MOCs. The TEM images show that the average length of MOOPs between two nearby armed points is 25.87 ± 1.79 nm (Figure 1i and Supporting Information, Figure S3). We observed specific lattice fringe, that is, the (220) plane of manganese oxide with the value of 1.58 Å, across this nanostructure (Figure 1j). The formation of MOOPs is probably due to the epitaxial growth process on the MOCs, which is clearly revealed by surveying the as-prepared product in the reaction system at a certain time interval (Supporting Information, Figure S4). The X-ray powder diffraction (XRD) pattern was employed to identify the crystallographic structure of all samples. MOOH, MOR, and MOOP nanostructures exhibit a typical MnO diffractogram pattern (JCPDS no. 01-072-1533), whereas MOCs nanoparticles show mixed MnO (JCPDS no. 01-0721533) and Mn3O4 (JCPDS no. 01-075-1560) diffractogram patterns (Figure 2a). These different crystallographic patterns could be ascribed to the partial oxidation from Mn2+ to Mn3+ in air, which has been proven by the previous research.48,49 Since
Figure 2. Crystal structure characterization of 0-D and 1-D MO nanostructures. (a) XRD pattern images of MOOHs, MORs, MOCs, and MOOPs, respectively. The XRD patterns can be assigned to the MnO phase (circular, JCPDS No. 01-072-1533) and Mn3O4 phase (triangle, JCPDS no. 01-075-1560). (b) XPS analyses of MOOHs, MORs, MOCs, and MOOPs, respectively. Compared to MOOHs, MORs, and MOOPs, the peak of the MOCs slightly shifts from the typical MnO to the Mn3O4 phase. These results indicate that MOOHs, MORs, and MOOPs are typically the MnO phase, while MOCs are a mixture phase of MnO and Mn3O4. 10458
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Figure 3. Dynamic growth process of MO nanostructures. TEM images of MO nanostructures withdrawn from the MOCs reaction solution after aging of (a) 10 min and (b) 15 min at 200 °C and (c) 10 min and (d) 40 min at 320 °C. TEM images of MO nanostructures withdrawn from the MOOPs reaction solution after aging of (e) 10 min at 200 °C and (f) 120 min, (g) 150 min, and (h) 180 min at 320 °C. TEM images of MO nanostructures withdrawn from the MOOHs reaction solution after aging of (i) 10 min, (j) 15 min, (k) 35 min, and (l) 60 min at 320 °C. TEM images of MO nanostructures withdrawn from the MORs reaction solution after aging of (m) 10 min at 200 °C and (n) 5 min, (o) 25 min, and (p) 60 min at 320 °C. These morphology evolutions indicate that the formation MOCs, MOOPs, and MOOHs are caused by the anisotropic growth, and that of MORs is caused by oriented attachment growth.
very first stage of any crystallization process, while it is hardly to be observed in TEM analysis.51 Thus, we analyzed the dynamic growth process of MO nanostructure after the nuclei formed by TEM and evaluated the dynamic thermal decomposition process of Mn−oleate by Fourier transform infrared spectroscopy (FT-IR). We observed the irregular crystal nuclei with the sizes of ∼3−6 nm in all samples after the aging time of 10 min in TEM images (Figure 3). Due to the higher nucleation temperature than other samples, the sizes of crystal nuclei in MOOH reaction solution are much larger than in the others. The successful formation of these crystal nuclei proves that 200 °C is high enough for the nucleation process. For the growth processes of MOCs, small quasi-spherical nanocrystals are generated after the nucleation process. With continuous consumption of the monomer at 320 °C, the nanostructure with cubic morphology formed. Besides, the size and uniformity of cubic nanostructures are all improved following the Ostwald ripening process along with the elapse of reaction time (Figure 3b−d). Additionally, FT-IR analyses show a gradual increase of the peak at 1711 cm−1, corresponding to the carboxyl group of oleic acid, along with the extension of reaction time (Supporting Information, Figure S5).37,52 Coupled with the
the size of the MOCs is significantly smaller than that of MOOHs, MORs, and MOOPs, MOCs exhibit much higher surface-to-volume ratio. This feature increases the oxidation probability of MOCs and leads to its mixture phase. Consistent with XRD analysis, the X-ray photoelectron spectroscopy (XPS) surveys in Mn 2p3/2 spectra show the partial oxidation of MOCs as well. The Mn 2p3/2 peaks of MOOHs, MORs, and MOOPs are measured at binding energies of 640.58, 640.36, and 640.41 eV, which agree with the value of MnO nanocrytals.50 Compared to MOOHs, MORs, and MOOPs, the peaks of MOCs slightly shift from the typical MnO pattern to the Mn3O4 pattern with the value of 641.03 eV (Figure 2b). These results indicate that the MOOHs, MORs, and MOOPs are a typical MnO phase, while MOCs are a mixture phase of MnO and Mn3O4. Formation Mechanism of Manganese Oxide Nanostructure from 0-D to 2-D. To understand the formation mechanism, careful analysis of samples taken from the reaction solution of each MO nanostructure at certain time intervals was conducted. The TEM analysis clearly indicates that the formations of different morphology nanostructures are highly dependent on the reaction condition. Nucleation represents the 10459
DOI: 10.1021/acs.chemmater.7b04100 Chem. Mater. 2017, 29, 10455−10468
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Figure 4. Controlled synthesis of 3-D MO nanostructures. TEM images of monodispersed (a) BMOAs, (b) SMOAs, and (c) MOWs, respectively. The higher magnification TEM images of (d) BMOAs, (e) SMOAs, and (f) MOWs, respectively. These results clearly show that the BMOAs, SMOAs, and MOWs are composed of many MO nanooctapods, nanopolyfacets, and curved nanowhiskers. HRTEM images of (g) BMOAs, (h) SMOAs, and (i) MOWs, respectively. The interplanar distances of 1.58 and 2.24 Å are assigned to the (220) and (200) planes of the MnO crystal.
ally, the morphology of a crystal can also be considered in terms of growth kinetics, by which the fast growth rate on one facet causes the disappearance of the facet and vice versa.55 The final morphology of a crystal could be controlled by introducing appropriate organic or inorganic agent to change the free energies to alter their growth rates and direction. The typical structure of MO nanocrystals is based on a cubic rock-salt structure with three low-energy facets, {100}, {110}, and {111}. The surface energies are following the order of {111} > {110} > {100} with the surface-energy ratio of 1, 1.41, and 1.73, respectively.56−58 Only using oleate as the surfactant, various crystal planes are equally capped and stabilized. Thus, the isotropic growth of crystal facets is dominated, resulting in the formation of MOSs.59,60 When the procedural heating up and Cl− ions are simultaneously introduced, anisotropic growth happened and formed MOCs. XPS survey in the Cl 2p spectrum shows the trace amount of Cl− ions on the surface of MOCs (Supporting Information, Figure S7). Since the exposed surface of MOCs is the {100} facet, this result suggests that the Cl− ions can bind to the manganese ions on the {100} plane.61 Thus, a possible Cl− ion assisted MOC formation mechanism is proposed. The relative low temperature caused by the procedural heating process leads to the polyfacets nucleus exposing a large amount of the {100} plane with the lowest surface energy on its surface. The Cl− ions can bind to the manganese ions on the {100} plane, resulting in the
successful formation of nuclei and growth of nanocrystals, these results clearly show the decomposition of Mn−oleate during the reaction. Surprisingly, dynamic growth processes of MOOPs are similar to those of MOCs. Along with the extension of reaction time of MOCs, the epitaxial growth process happened and formed the MOOPs (Figure 3e−h). For the growth of MOOHs, we noticed the formation of octahedron and tetrahedron nanostructure after reaction for 35 min (Figure 3k). On the basis of that the surfaces of octahedral and tetrahedron MO nanostructure are enclosed by the {111} plane, and this result may reveal that the chloride ions prefer to bind to manganese ions on the {111} plane with high metal ion package density and surface energy at high temperature. Interestingly, the TEM images of the product taken from the reaction solution of MORs clearly showed the self-assembly process along a specific direction, especially the product took at an aging time of 5 min at 320 °C (Figure 3m− p). These results indicate that the anisotropic growth of MORs may proceed by the oriented attachment mechanism. On the basis of TEM analysis results, a formation mechanism of 0-D and 1-D anisotropic MO nanostructures was proposed (Supporting Information, Figure S6). The morphology of a crystal is dependent on the specific surface energies associated with the facets of the crystal. Based on the well know Wulff facets theory, a crystal has to be bounded by facets giving a minimum total surface energy when it is stable.53,54 Addition10460
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Figure 5. Analyses the assembled process of BMOAs and MOWs. TEM images of (a−c) BMOAs and (d−f) MOWs withdrawn from reaction solution after aging different times during the growth process. These results clearly show that the formation of BMOAs and MOWs is based on the self-assembly crystal growth and secondary growth.
preservation of the {100} plane and formation of MOCs in the further heating up process. Along with the increase of the reaction time, the amount of chloride ions is sufficient to preserve the {100} plane and results in the epitaxial growth on the MOCs to form the MOOPs.43 Without adding chloride ions, the temperature drop caused by the procedural heating process may slow down the growth of the nuclei.42 When two nanoparticles approach each other closely enough, they are mutually attracted by van der Waals forces. Along with the rapid rise of reaction temperature again, the strength to eliminate the high energy surface of the pairs will drive a substantial reduction in the surface free energy by sharing a common crystallographic orientation and form the MORs by oriented attachment growth.62 Without applying the procedural heating process, the decomposition rate of the Mn−oleate and nucleation improved due to the high reaction temperature (320 °C), resulting in the increase of the proportion of the {111} facet on the polyfacet surface. Since the {111} plane exhibits the highest metal package density and lowest attachment energy among the basic planes, the absorption of chloride ions on the manganese oxide {111} facet is more favorable than others in thermodynamics. The XPS analysis on MOOHs in Cl 2p shows a typical peak of the Cl element (Supporting Information, Figure S7). On the basis of the fact that the exposed surface of the MOOHs is the {111} plane, this results indicate that the introduced Cl− ions can bind to the manganese ions on the {111} facet at high nucleation temperature and assist the formation of MOOHs.61 Synthesis and Characterization of 3-D Manganese Oxide Nanostructure. To obtain the 3-D MO nanostructures, we synthesized MO nanostructure with the procedural heating process in phenyl ether in either the presence or the absence of chloride. It is worthwhile to note that the boiling temperature of phenyl ether is lower than that of ODE, which may slow down the growth of nuclei and promote their assembly. We first demonstrated that a uniform 3-D branched MO nanoassembled (BMOAs) structure can be obtained by
adding chloride. The edge lengths of these nanoassembled structures are approximate 120.47 ± 7.98 nm (Figure 4a and Supporting Information, Figure S8). After carefully surveying this unique 3-D nanostructure, we found that the morphology of this 3-D nanostructure is similar to the morphology of nanooctapod assembled nanoclusters (Figure 4d).43 To better visualize the structure, we analyzed these 3-D nanostructures by HRTEM. The HRTEM images reveal the uniform lattice fringes with the length of 1.58 Å, that is, the (220) plane of manganese oxide (Figure 4g). More importantly, the HRTEM images clearly showed a sharp edge, which is the same as that of the octapod nanocrystal, and prove the assembled units may be the octapod MO nanoseeds. We have further investigated the growth process of this 3-D nanostructure by analyzed the samples taken from the reaction solution. The TEM images obviously showed the process that pairs of octapod nanoseeds attached to each other to reduce the surface free energy and form the unique 3-D nanostructure. Additionally, we observed several irregular nanostructures caused by the secondary growth of octapod nanoseeds, which can be ascribed to the high monomer concentration (Figure 5a−c). Interestingly, under the similar procedure with a reduced chloride amount, an assembled 3-D MO nanostructure with nearly spherical morphology formed (Figure 4b). Further TEM and HRTEM analysis showed that the edge length of this 3-D spherical MO nanoassembled structure (SMOAs) is about 100.52 ± 6.23 nm with the interplanar spacing distances of 1.58 Å, that is, the (220) plane of manganese oxide (Figure 4e,h and Supporting Information, Figure S8). In addition, the HRTEM images reveal that the SMOAs are composed of many small nanoseeds with polyfacets, which is different from BMOAs and causes the differences in morphologies. Surprisingly, without adding chloride, we obtained 3-D MO nanowhiskers (MOWs). TEM analysis indicates that MOWs are highly uniform and composed of many curved nanowhiskers (Figure 4c). The aspect ratios of each nanowhisker are approximately 20 (with the length of 103.50 ± 7.14 nm and width of 5.11 ± 0.21 nm), 10461
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Chemistry of Materials
Figure 6. Crystal structure characterization of 3-D MO nanostructures. (a) XRD pattern images of BMOAs, SMOAs, and MOWs, respectively. The XRD patterns can be assigned to the MnO phase (JCPDS No. 01-072-1533), indicating their MnO phases. XPS analyses of (b) BMOAs, (c) SMOAs, and (d) MOWs, respectively. Consistent with the XRD analyses, BMOAs, SMOAs, and MOWs show that the valencesof manganese ions in the BMOAs, SMOAs, and MOWs are +2.
However, the field-independent magnetization (M−H) curves show that the magnetic moments of all MO nanostructures reveal the linear growth trend with the increase of applied magnetic field (Figure 7a,b). Moreover, all samples exhibit nearly zero values for both coercivity and remanence at 300 K, indicating that all MO nanostructures exhibit paramagnetic behavior at room temperature (Figure 7c,d). This phenomenon could be ascribed to the presence of uncompensated spins on the particle surface.37,65 For MOOHs, MOCs, and MOOPs, the unsaturated magnetic moments reach 1.61, 1.92, and 1.78 emu/ g under a magnetic field of 5 T at 300 K, respectively. These differences on the magnetization values could be ascribed to the different noncompensated surface spins. Theoretically, the MO nanstructures with higher surface-to-volume ratio on the surface exhibit a larger amount of noncompensated surface spin and higher magnetization values.37 The surface-to-volume ratios of MOOHs, MOCs, and MOOPs are 0.34, 0.67, and 0.41 nm−1, respectively. Thus, MOCs exhibit the highest magnetization values among the 0-D nanostructures. Similarity with 0D MO nanostructures, the SMOAs, BMOAs, and MOWs in 3D exhibit the increased unsaturated magnetic moments with the values of 2.08, 2.19, and 2.43 emu/g, respectively, due to the increased noncompensated surface spins. Additionally, temperature dependence of the magnetization of all samples was measured with zero-field-cooling (ZFC) and field-cooling (FC) procedures in an applied magnetic field of 100 Oe in the temperature range 5−300 K. The ZFC/FC analyses clearly show that all MO nanostructures show obvious phase transition from ferromagnetic to paramagnetic phases at the relatively low temperature. Due to the increase of noncompensated surface
which is between the values of the nanorod and nanowire (Supporting Information, Figure S8). After carefully surveying these unique nanostructures, we found that most nanowhiskers have two branches even if some display 3, 4, or 5 branches (Figure 4f). Based on the TEM images of the intermediate products taken from the reaction solution, the formation of this assembled nanowhisker may be caused by the oriented attachment (Figure 5d−f). It should be noted that all the nanowhiskers are single-crystalline as evidenced by the HRTEM analysis. The HRTEM images show the uniform lattice fringes with the length of 2.24 Å, that is, the (200) plane of manganese oxide (Figure 4i). We then employed the XRD pattern to identify the crystallographic structure of all 3-D MO nanostructures (Figure 6a). All samples exhibit a typical MnO diffractogram pattern (JCPDS no. 01-072-1533). Consistent with XRD analysis, the XPS surveys in Mn 2p3/2 spectra show that the valences of manganese ions in the BMOAs, SMOAs, and MOWs are +2. The Mn 2p3/2 peaks of BMOAs, SMOAs, and MOWs are measured at binding energies of 640.38, 640.48, and 640.38 eV, which are in agreement with the value of MnO nanocrytals (Figure 6b−d). These results indicate that the BMOAs, SMOAs, and MOWs are the typical MnO phase. Magnetic Property of Manganese Oxide Nanostructures. Magnetic properties of all 0-D, 1-D, and 3-D MO nanostructures were investigated at room temperature (300 K) by the superconducting quantum interference device (SQUID) magnetometer. Due to the superexchange interactions between neighboring Mn2+ cations, bulk MnO nanoparticles is a classical antiferromagnet with Neel temperature (TN) of 100 K.63,64 10462
DOI: 10.1021/acs.chemmater.7b04100 Chem. Mater. 2017, 29, 10455−10468
Article
Chemistry of Materials
Figure 7. Analyses of the magnetic properties of different MO nanostructures. The smooth M−H curves of (a) 0-D and 1-D and (b) 3-D MO nanostructures measured at 300 K using a superconducting quantum interference device magnetometer. The M−H curves of (c) 0-D and 1-D and (d) 3-D MO nanostructures in low-magnetic field areas, showing nearly zero values for both coercivity and remanence and indicating that all MO nanostructures exhibit paramagnetic behavior at room temperature. The ZFC/FC curves of (e) 0-D and 1-D and (f) 3-D MO nanostructures measured under an applied magnetic field at 50 Oe, further confirming their paramagnetic behavior at room temperature.
prepared MO nanostructures are hydrophobic and unsuitable for surveying their T1 contrast abilities, we transferred all the nanostructures to aqueous media by small molecular dopamine to form a thin-layer coating on the surface. This thin-layer coating can not only endow the good water solubility but also provide proton abundant environment to the nanostructure, which are critically important to producing the MRI contrast signal.10,63 The transferred nanostructures are stable in water without precipitation for at least 1 month. TEM analyses further confirm that the transferred nanostructures are well dispersed in water without any clustering or aggregation (Supporting Information, Figure S9). We then focused on the T1 relaxation shortening capacities of all obtained MO nanostructures by a 0.5 T MRI scanner. Interestingly, the MO nanostructures with different crystal structures exhibit different T1 relaxivities. The r1 values of MOOHs, MORs, MOCs, MOOPs, BMOAs, SMOAs, and MOWs are 1.56, 0.48,
spin, the blocking temperature (TB) values of MOOHs, MOOPs, and MOCs increase with the values of 15.99, 20.09, and 21.98 K, respectively (Figure 7e). Interestingly, the MOR, BMOA, SMOA, and MOW growth by oriented attachment exhibits much higher TB than 0-D MO nanostructures with the values of 65.03, 40.02, 34.01, and 50.02 K, respectively (Figure 7f). These phenomena could be ascribed to their multicore structures caused by the oriented attachment growth. Although all MO nanostructures show different TB, their TB values are all below 300 K, indicating the paramagnetic behaviors at room temperature and enabling these MO nanostructures for biomedical application. Shortening Effect of MO Nanostructures on the Proton Spin−Lattice Relaxation. Recently, biocompatible MO nanoparticles were proposed as a new T1 MRI contrast agent. However, the inner relationship between the crystal structures and T1 contrast abilities is unclear. Due to the as10463
DOI: 10.1021/acs.chemmater.7b04100 Chem. Mater. 2017, 29, 10455−10468
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Chemistry of Materials
Figure 8. T1 MRI relaxivities of MO nanostructures and MRI contrast imaging in vitro and in vivo. (a) The comparisons of r1 values and r2/r1 ratios of MOOHs, MORs, MOCs, MOOPs, BMOAs, SMOAs, and MOWs, respectively. Since the surface coating ligand is the same, these results indicate that the T1 relaxivities of MO nanostructures are highly dependent on their crystal structures. (b) The comparisons of surface-to-volume ratio and T1 relaxivity and (c) metal package model of the MnO {111}, {110}, and {100} facets. These results indicate that the T1 relaxivities are affected by the surface-to-volume ratio and magnetic ion density on the surface. (d) T1 MRI phantom studies of all MO nanostructures at different Mn concentrations (mM) in 1% agarose at 0.5 T. (e) T1-weighted MR images of HepG2 cells incubated with MOCs for different time durations. (f) Total amount of Mn ions in HepG2 cells incubated with MOCs for different times. The concentration of Mn ions was tested by ICP-MS (**p < 0.01, n = 3/group). (g) In vivo MR images of BALB/c mice at 0 and 1 h after intravenous injection of MOCs (2 mg Mn kg−1) at the coronal (upper) and transverse (lower) planes. These results indicate that MOCs possess a significantly higher T1 signal in the liver region. (h) Quantification of relative liver contrast collected at different times after administration of MOCs (**p < 0.01, n = 3/group).
11.50, 1.89, 0.46, 0.42, 2.26 mM−1 s−1, respectively (Figure 8a and Supporting Information, Figure S10 and Table S1). Since the surface coating ligand is the same, the different r1 values could be attributed to their different crystal structures. To simplify the investigation on the inner-relationship between the T1 shortening effect and the crystal structure of the MO nanostructures, we divided all nanostructures into two parts based on their complexities. One is the 0-D and 1-D nanostructure, and the other is the 3-D nanostructure. Interestingly, we found that the r1 values of the 0-D and 1-D MO nanostructures are highly dependent on their surface-tovolume ratio. The surface-to-volume ratios of MOCs, MOOPs, MOOHs, and MORs were calculated to be 0.67, 0.41, 0.34, and 0.17 nm−1 (Figure 8b and Supporting Information, Table S1). Along with the decrease of surface-to-volume ratio, the T1 relaxation of MOCs, MOOPs, MOOHs, and MORs exhibited the obvious reduction with the values of 11.50, 1.89, 1.56, and 0.48 mM−1 s−1. These results could be ascribed to the fact that the surface-to-volume ratio can mainly determine the surface exposed paramagnetic ions number. Theoretically, the T1 relaxation enhancement is mainly related to the inner sphere regime that protons achieve chemical exchange with the surface paramagnetic ions directly. Thus, the higher the surface-tovolume ratio, the more paramagnetic ions are exposed on the surface and the higher the T1 relaxation enhancement capacity exhibit.66,67 Additionally, we noticed that MO nanostructures with metal rich surface may possess high density of accessible
metal ions, fast exchange of water, and multicenter coordination for water molecules, which can further improve its high T1 relaxivity (Figure 8c).68 To verify this inference, MOCs with the {100} facet exposed and MOOHs with the {111} facet exposed were chosen as representative examples. Accordingly, MOSs with mean diameters of 9 and 18 nm (denoted as MOSs-9 and MOSs-18) were used for comparison because of the similarity in surface-to-volume ratios (that is, MOCs with MOSs-9 and MOOHs with MOSs-18). Since the {100} facet of the MO nanostructure is a metal-rich surface, the manganese ions density on the surface of the MOCs exposed {100} facet is much higher than that on the MOSs-9 with the mixed exposed facet. MOCs manifest T1 contrast effects exceptionally stronger than those of MOSs-9. The r1 value of MOCs is 11.50 mM−1 s−1, which is approximate 2.64 times higher than that of MOSs9 (4.46 mM−1 s−1). Similarly, the MOOHs exposed (111) facet shows a slightly higher r1 value than MOSs-18 with the value of 1.28 mM−1 s−1 (Supporting Information, Figure S11 and Table S2). These results indicate that MO nanostructures with high surface manganese ion intensity can further improve their T1 relaxivities. It is worthwhile to note that the increment of r1 values caused by MOOHs is lower compared to the r1 value improvement caused by MOCs. These results could be attributed to its relatively low surface-to-volume ratio, which results in the proportion of manganese ions on the surface of MOOHs being significantly lower than that of MOCs and limits the improvement. For the 3-D MO nanostructures, the 10464
DOI: 10.1021/acs.chemmater.7b04100 Chem. Mater. 2017, 29, 10455−10468
Article
Chemistry of Materials
time-dependent T1 signal changes reflected the uptake process of MOCs by HepG2 cells. The total amounts of Mn ions in the cells before and after treatment were also measured by inductively coupled plasma mass spectrometry (ICP-MS). It appears that the cells treated by PBS for 3 h contained 186.43 ng of Mn ions, likely due to Mn being a natural cellular constituent and acting as a cofactor for enzymes.73,74 Remarkably, the amount of Mn ions in cells dramatically increased to 202.62, 393.09, and 870.37 ng after incubation with MOCs for 0.25, 1.5, and 3 h, further confirming that the change of T1 signal is caused by the uptake of MOCs by cells (Figure 8f). To further evaluate the ability of MOCs for in vivo imaging, we performed the T1-weighted MRI contrast imaging using BALB/c mice as a model in vivo by a 7 T MRI scanner. Because of the high enrichment of nanomaterials in the liver, we focused on the liver as the targeted region. After intravenous injection of MOCs or MOSs-9 at a dose of 2 mg Mn/kg of mouse body weight, we indeed observed significant signal attenuation in the liver region at 1 h postinjection (p.i.) at both coronal and transverse planes (Figure 8g). Since the MOSs-9 show lower r1 value than MOCs, the T1 signal enhancement in the liver region of mice treated by MOSs-9 is much weaker than that of the mice treated by MOCs (Supporting Information, Figure S14). To quantify the contrast, we identified the liver as the region of interest (ROI) and calculated the signal-to-noise ratio (SNR) and SNRpost/SNRpre values. It appears that the MR signal changes (ΔSNR) in the liver region are as high as 68.58 and 78.04% at the coronal and transverse planes for the mice treated by MOCs, respectively, which are significantly higher than those of mice treated by MOSs-9 (Figure 8h and Supporting Information, Figure S14 and Table S4). These results demonstrated that MOCs have the ability to show strong MR contrast enhancement in T1 imaging in vivo, which may be a potential candidate to assist early and accurate lesion detection in T1-weighted MRI contrast imaging, particular in the liver.
surface-to-volume ratio decreases with the increase of size. Besides, the secondary growth blocks the path of the proton to enter into the inside spaces of BMOAs and SMOAs, which further reduce their T1 relaxivities. The r1 values of BMOAs and SMOAs are remarkably lower than that of 0-D MO nanostructures with the values of 0.46 and 0.42 mM−1 s−1. It is worthwhile to notice that the MOWs reveal the comparable T1 relaxivity with the value 2.26 mM−1 s−1 to 0-D MO nanostructures due to the geometrical confinement. In theory, T1 relaxivity is highly dependent on certain properties of the T1 contrast agent, such as molecular tumbling time (τD). Ideally, long τD benefits the chemical exchange between water and magnetic ions and achieves strong T1 relaxation shortening effect. Compared to the BMOAs and SMOAs, the stretched nanowhiskers allow the proton to enter into the inside space of MOWs. More importantly, the specific structure of nanowhiskers can produce confined space to restrict diffusion of water proton in it, which can increase the τD in the inner sphere and improves its T1 contrast enhancement.69,70 Concurrently, the r2/r1 ratio is an important reference to decide whether a given contrast agent is suited to T1 MRI contrast imaging. To investigate the T1 contrast imaging ability of different MO nanostructures, we evaluated the r2/r1 ratio of all samples. The r2/r1 ratios of MOOHs, MORs, MOCs, MOOPs, BMOAs, SMOAs, and MOWs are 2.81, 5.21, 1.71, 3.05, 6.24, 6.79, and 4.01, respectively (Figure 8a and Supporting Information, Figure S12 and Table S3). On the basis of the fact that the low r2/r1 ratio (
