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Article Cite This: ACS Appl. Nano Mater. 2018, 1, 145−151

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Magnetic Upconversion Luminescent Nanocomposites with Small Size and Strong Super-Paramagnetism: Polyelectrolyte-Mediated Multimagnetic-Beads Embedding Yadan Ding,†,‡ Xia Hong,*,†,‡ Peng Zou,†,‡ Kai Liu,‡ Tie Cong,† Hong Zhang,*,‡ and Yichun Liu† †

Key Laboratory of UV-Emitting Materials and Technology (Northeast Normal University), Ministry of Education, Changchun 130024, P. R. China ‡ Van’t Hoff Institute for Molecular Sciences, University of Amsterdam, Science Park 904, 1098 XH Amsterdam, The Netherlands

ACS Appl. Nano Mater. 2018.1:145-151. Downloaded from pubs.acs.org by 5.62.152.179 on 01/04/19. For personal use only.

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ABSTRACT: The incorporation of magnetic and upconversion luminescent properties into one single nanostructure is highly desirable in nanomedicine for contrast agents and/or nanotheranostic platforms. Current magnetic upconversion luminescent nanocomposites generally suffer from relatively large size and/or low magnetization, which might induce unsatisfactory colloidal stability, reticuloendothelial system clearance, and limit their applications in biolabeling, sensing, imaging, bioseparation, magnetic targeting, and so on. Herein, we constructed multimagnetic-beads-embedded Fe3O4/NaYF4: Yb, Er nanocomposites to overcome these problems. Polyelectrolyte was introduced as an organic intermediate layer to offset the crystal lattice mismatch between Fe3O4 and NaYF4: Yb, Er. It also acted as the ligand to direct the growth of NaYF4: Yb, Er on the surface of Fe3O4. So-prepared nanocomposites exhibited an average size of 33.8 nm, much smaller than those with magnetic nanoparticle clusters as the core. The saturation magnetization of the nanocomposites is 17.8 emu/g, higher than those following current single magnetic nanoparticle embedded approach. To demonstrate their application potential in bioimaging and theranostics, magnetic field-assisted sensitive upconversion luminescence cell imaging is presented. KEYWORDS: superparamagnetism, upconversion luminescence, nanocomposite, polyelectrolyte, cell imaging



INTRODUCTION Nanocomposite materials, which can integrate multiple functionalities into one single nanosystem, have been a research hotspot in the past years. 1,2 Among them, magnetic upconversion luminescent nanocomposites have attracted considerable attention in various biomedical fields.3−5 The magnetic component enables convenient targeted enrichment and separation of the nanocomposites as well as magnetic targeted drug delivery.6−8 It also renders magnetic resonance imaging (MRI) with high spatial resolution and deep penetration depth for in vivo imaging, but it suffers from limited sensitivity and resolution for imaging at the cellular level.9,10 Upconversion luminescent nanomaterials, which can convert low-energy near-infrared (NIR) excitation light into high-energy visible/NIR emission light, have many advantages over traditional phosphors in large anti-Stokes shift, narrow emission bandwidths, negligible photobleaching, low autofluorescence background, and deep tissue penetration of the excitation light.11,12 These unique properties promote upconversion luminescent nanomaterials in biochemical sensors, immunoassays, therapies, and particularly, background-free bioimaging even at cellular or subcellular level.13−19 Therefore, the incorporation of magnetic and upconversion luminescent properties into one single nano© 2017 American Chemical Society

structure is highly desirable in nanomedicine to improve targeting efficiency and enable MRI and optical dual imaging in deep tissue. During the past decade, some magnetic upconversion luminescent nanocomposites have been constructed and have shown great potential in biomedical applications.20−23 For example, by using SiO2-assisted synthetic strategy, Zhang et al.23 synthesized upconversion luminescent and magnetic nanorattles with a diameter of ∼115 ± 20 nm and saturation magnetization of 1.28 emu/g via an ion-exchange process. The nanorattle consists of an Fe3O4 magnetic core with the diameter of ∼20 ± 10 nm, a silica layer with the thickness of ∼10 ± 5 nm, an intervening hollow space, and a NaYF4/Yb, Er shell with the thickness of ∼20 ± 10 nm. The hollow nanorattles loaded with antitumor drug exhibited excellent cell imaging properties and showed enhanced in vivo therapy efficacy of tumor under an external magnetic field. Cross-linker anchoring strategy and polymer encapsulation method have also been developed to incorporate preformed magnetic nanoparticles and upconversion nanoparticles.24−27 These Received: October 18, 2017 Accepted: November 30, 2017 Published: November 30, 2017 145

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Scheme 1. Schematic Illustration of the Synthetic Procedures of the Water-Dispersible Fe3O4/NaYF4: Yb, Er Nanocomposites

for 1 h. Afterward, it was further heated to 300 °C and maintained that temperature for another 1 h. After it cooled to room temperature, the product was collected by magnetic enrichment and washed with ethanol three times. The obtained Fe3O4 nanoparticles dispersed in hexane were then transferred to ethylene glycol via PEI coating following the protocols described in our previous report,35 where the nanoparticles were finally dispersed in water instead of ethylene glycol. Preparation of Fe3O4/NaYF4: Yb, Er Nanocomposites. Fe3O4/ NaYF4: Yb, Er nanocomposites were prepared following the previously reported synthetic procedures of NaYF4: Yb, Er nanoparticles with modification.36 Briefly, 0.480 mmol of YCl3, 0.108 mmol of YbCl3, 0.012 mmol of ErCl3, and 1.200 mmol of NaCl were dissolved in 9 mL of ethylene glycol by magnetic stirring. Then, it was mixed with 6 mL of ethylene glycol solution containing 6.000 mmol of NH4F and 0.150 g of PEI and stirred for 10 min. Subsequently, 400 μL of Fe3O4 nanoparticles in ethylene glycol (10 mg/mL) was mixed into the above solution via sonication treatment. The mixture was then transferred to a Teflon-lined autoclave and reacted for 2 h at 200 °C. After they cooled to room temperature, the Fe3O4/NaYF4: Yb, Er nanocomposites were collected by centrifugation and magnetic enrichment along with ethanol scrubbing. The obtained nanocomposites were dispersed in water. Cytotoxicity Study. The cytotoxicity of Fe3O4/NaYF4: Yb, Er nanocomposites on human breast cancer MCF-7 cells and mouse fibroblast 3T3 cells was evaluated by the standard thiazolyl blue tetrazolium bromide (MTT) assay. The cells (100 μL) were seeded into 96-well plates with the concentration of 5 × 104/mL and incubated at 37 °C under 5% CO2. After 24 h, 100 μL of the Fe3O4/ NaYF4: Yb, Er nanocomposites dispersed in the culture medium was added into the wells with a final concentration of 0, 5, 20, 50, 200, and 500 μg/mL. The cells were incubated with the nanocomposites for 24 h, followed by the removal of the culture medium and the rinsing of the 96-well plates with phosphate-buffered saline. Subsequently, 100 μL of the culture medium and 10 μL of MTT solution (5 mg/mL in phosphate buffered saline) were added to each well and incubated for 4 h. After the culture medium was removed, 100 μL of isopropyl alcohol was added to each well and reacted for 2 h. The OD values at 550 nm were recorded with a microplate reader and used to calculate the cell viability. All the values of cell viability are presented as average value ± standard deviation. Confocal Imaging. MCF-7 cells and 3T3 cells were seeded on a coverslip with the concentration of 1 × 104 cells/mL. After 24 h, the cells were incubated with the Fe3O4/NaYF4: Yb, Er nanocomposites (5 μg/mL or 200 μg/mL) for 3 h at 37 °C. After they were washed three times with phosphate-buffered saline, the cells were fixed with 4% paraformaldehyde and mounted with 95% glycerol solution. Upconversion luminescence imaging was then performed with confocal microscope system. Characterizations. The morphologies of the nanoparticles were characterized by a transmission electron microscope (TEM, JEOL JEM-2100). High-resolution transmission electron microscope (HRTEM) images were acquired under an acceleration voltage of 200 kV. The structures of the nanoparticles were characterized by an X-ray powder diffractometer (XRD, Rigaku D/MAX 2500) with Cu Kα radiation (λ = 0.1541 nm, 50 kV, 300 mA). The elemental composition of the nanocomposites was characterized by X-ray photoelectron spectroscopy (XPS) using a Thermo ESCALAB 250

excellent works have provided important guidance for the fabrication of magnetic upconversion luminescent nanocomposites and demonstrated their great values in biomedical applications. The limit of these strategies is that the synthesized nanocomposites generally suffer from large size (from 60 nm to hundreds of nanometers) and/or low magnetization (less than 10 emu/g), which might induce unsatisfactory colloidal stability, reticuloendothelial system clearance, and limit their applications in biolabeling, sensing, imaging, bioseparation, magnetic targeting, and so on.5,9,10,28 Although small-sized magnetic upconversion luminescent nanocomposites can be obtained through seed-induced growth method,10,29,30 the single-magnetic-core structure results in a low saturation magnetization. Fe3O4 nanoparticle clusters (∼180 nm or larger) can been used as the magnetic core to prepare magnetic upconversion luminescent nanocomposites with the magnetization higher than 15 emu/g;31−33 however, the size of the nanocomposites tends to increase to over 200 nm. It still remains a challenge to obtain magnetic upconversion luminescent nanocomposites with relatively small size and high magnetization, which is of vital importance for their biomedical applications. Inspired by the above works,10,29−33 we herein designed and fabricated multimagnetic-beads-embedded Fe3O4/NaYF4: Yb, Er magnetic upconversion luminescent nanocomposites with polyelectrolyte-coated Fe3O4 nanoparticles as the seeds. The polyelectrolyte can serve not only as a “soft” intermediate layer to offset the crystal lattice mismatch between Fe3O4 and NaYF4: Yb, Er but also as the ligand to direct the growth of NaYF4: Yb, Er on the surface of Fe3O4. The crystal structure, morphology, magnetic, and upconversion luminescent properties of the Fe3O4/NaYF4: Yb, Er nanocomposites were studied. After the cytotoxicity of the nanocomposites on human breast cancer MCF-7 cells and mouse fibroblast 3T3 cells was evaluated, the performance of the magnetic upconversion luminescent nanocomposites on cell imaging was also investigated.



EXPERIMENTAL SECTION

Chemicals. Benzyl ether, oleic acid, oleylamine, iron(III) acetylacetonate [Fe(acac)3] and branched polyethylenimine (PEI, Mw ≈ 25 000) were purchased from Sigma-Aldrich. 1,2-Hexadecanediol was purchased from TCI (Shanghai) Development Co., Ltd. YCl3 (99.99%), YbCl3 (99.99%), and ErCl3 (99.99%) were purchased from Beijing Zhongjinyan New Material Technology Co., Ltd. NaCl (99%), ethylene glycol (99%), hexane, and ethanol (99%) were purchased from Beijing Chemical Works. NH4F was purchased from Sinopharm Chemical Reagent Co., Ltd. All of the chemicals were used as received. Preparation of Fe3O4 Nanoparticles. Fe3O4 nanoparticles were prepared according to the literature with some modifications.34 First, 2.584 g of 1,2-hexadecanediol, 1.436 g of Fe(acac)3, 4.244 mL of oleic acid, 4.586 mL of oleylamine, and 40 mL of benzyl ether were mixed under nitrogen flow. Then, the mixture was heated to 200 °C and kept 146

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ACS Applied Nano Materials instrument. The magnetic property of the nanoparticles was measured by a superconducting quantum interference device (SQUID) magnetometer (Quantum Design MPMS-XL) at 300 K. Luminescence spectra were recorded with an LS-55 PerkinElmer luminescence spectrometer under the excitation of an external 980 nm diode laser. Fourier transform infrared (FTIR) spectra were recorded with Nicolet 6700 FTIR spectrometer. Zeta potential was determined with a Malvern Zetasizer Nano system (Nano ZS90). Upconversion luminescence imaging was acquired with our confocal microscope system,37 where the 980 nm irradiation power density of ∼100 W/cm2 was used. There was no damage of the cells observed, which may be ascribed to the fast scanning during the imaging (∼20 Hz).38



RESULTS AND DISCUSSION Synthesis Strategy of the Fe3O4/NaYF4: Yb, Er Nanocomposites. The Fe3O4/NaYF4: Yb, Er nanocomposites were synthesized with Fe3O4 nanoparticles serving as the seeds, as illustrated in Scheme 1. Oleate-capped Fe3O4 nanoparticles were first prepared by thermal decomposition of Fe(acac)3 in high boiling point organic solvents. Because of the lattice mismatch between Fe3O4 and NaYF4: Yb, Er, PEI, a wellknown polyelectrolyte with great potential in gene delivery, neuronal growth studies, and some other biomedical applications39−43 was then coated on the oleate-capped Fe3O4 nanoparticles via ligand exchange to serve as an organic intermediate layer. It also renders the Fe3O4 nanoparticles dispersible in ethylene glycol. PEI was chosen because of its high coordinating capacity with various nanomaterials and its good solubility in polar solvents. Its high molecular weight and hyperbranched structure also render it suitable to serve as an organic buffer layer between Fe3O4 and NaYF4: Yb, Er. When mixing with the reaction precursors of NaYF4: Yb, Er in ethylene glycol, the polyelectrolyte-stabilized Fe3O4 nanoparticles can serve as the seeds for the subsequent solvothermal growth of NaYF4: Yb, Er in a ligand-directing manner, which might initiate from the coordination interaction between the amine groups of the polyelectrolyte and the rare-earth ions in the reaction solution. Driven by the magnetic dipole−dipole interaction, several adjacent Fe3O4 nanoparticles might be wrapped into one nanoparticle via the gluing of growing NaYF4: Yb, Er. It is worth noting that an appropriate amount of Fe3O4 nanoparticles was needed for the formation of the multimagnetic-beads-embedded structure, avoiding either selfnucleation of NaYF4: Yb, Er or incomplete coating of Fe3O4. Morphology and Crystal Structure of the Fe3O4/ NaYF4: Yb, Er Nanocomposites. One typical TEM image of the as-prepared Fe3O4 nanoparticles is shown in Figure 1a. It can be seen that the nanoparticles are in spherical shape, and the average size is ∼5.8 nm with a narrow size distribution. The Fe3O4/NaYF4: Yb, Er nanocomposites exhibit cubic shape with an average size of ∼33.8 nm (Figure 1b). Some small bright dots can be observed clearly in the nanocomposites. Their average size is ∼5.3 nm, implying that they might be Fe3O4 nanoparticles. HRTEM images were recorded to further provide the structural information on the nanocomposite. As shown in Figure 1c, the interplanar spacing of the lattice fringes in the dark “area 1” and bright “area 2” is 0.31 and 0.21 nm, respectively, which corresponds to the (111) plane of NaYF4 and (400) plane of Fe3O4, respectively. The fast Fourier transform (FFT) results of these two areas are shown on the right side of Figure 1c. They are indexed to face-centered cubic (fcc)-structured NaYF4 and fcc-structured Fe3O4, respectively. Some blurred areas between the bright area and the dark area are present in Figure 1c. No apparent lattice fringes can be

Figure 1. TEM images of (a) the Fe3O4 nanoparticles and (b) the Fe3O4/NaYF4: Yb, Er nanocomposites. (c) HRTEM image of the Fe3O4/NaYF4: Yb, Er nanocomposite and the corresponding FFT patterns.

observed in those areas, probably due to the existence of amorphous polyelectrolyte intermediate layer capped on the surface of the Fe3O4 nanoparticles. These results demonstrate the formation of multicore structured Fe3O4/NaYF4: Yb, Er nanocomposites. The crystal structures of the as-prepared Fe3O4 nanoparticles and Fe3O4/NaYF4: Yb, Er nanocomposites were also studied by XRD technique. As presented in Figure 2a, the diffraction peaks

Figure 2. XRD patterns of (a) the Fe3O4 nanoparticles and (b) the Fe3O4/NaYF4: Yb, Er nanocomposites. (*) The diffraction peaks from Fe3O4.

of the Fe3O4 nanoparticles (Figure 2a) agree well with inverse spinel structured Fe3O4 (JCPDS card No. 75−1610). The additional diffraction peaks observed in Figure 2b can be indexed to cubic phased NaYF4 (JCPDS card No. 77−2042), indicating the successful incorporation of Fe3O4 and NaYF4: Yb, Er. The weak diffraction signals from Fe3O4 can be 147

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Figure 3. (a) Hysteresis loops of the Fe3O4 nanoparticles and the Fe3O4/NaYF4: Yb, Er nanocomposites. (b) Upconversion luminescence spectrum of the Fe3O4/NaYF4: Yb, Er nanocomposites. (c) Visualized presentation of magnetic property and upconversion luminescent property of the Fe3O4/NaYF4: Yb, Er nanocomposites with magnet and/or 980 nm laser irradiation.

Surface Properties of the Fe3O4/NaYF4: Yb, Er Nanocomposites. Good water dispersibility is a prerequisite for most biomedical applications of nanomaterials. It is mainly determined by the surface properties of the nanomaterials. Therefore, we characterized the synthesized Fe3O4/NaYF4: Yb, Er nanocomposites by FTIR technique, which can provide important structural information about their surface. As shown in Figure 4, three main vibrational bands centered at ∼3430,

attributed to its small size and limited content in the nanocomposite. The presence of Na, Fe, F, O, N, C, and Y elements in the XPS pattern (Figure S1) further confirmed the formation of the nanocomposites with polyelectrolyte incorporated. Magnetic and Upconversion Luminescent Properties of the Fe3O4/NaYF4: Yb, Er Nanocomposites. The magnetic and upconversion luminescent properties of the Fe3O4/NaYF4: Yb, Er nanocomposites were also investigated. The hysteresis loops of the Fe3O4 nanoparticles and the Fe3O4/ NaYF4: Yb, Er nanocomposites measured at 300 K are shown in Figure 3a. The absence of hysteresis indicates the superparamagnetism of both the Fe3O4 nanoparticles and the Fe3O4/ NaYF4: Yb, Er nanocomposites. Although the saturation magnetization decreased from 56.1 emu/g of the Fe3O4 nanoparticles to 17.8 emu/g of the nanocomposites resulting from the incorporation of nonmagnetic NaYF4: Yb, Er component, the saturation magnetization of the multimagnetic-beads-embedded nanocomposites was still higher than that of many other reported single-magnetic-core magnetic upconversion luminescent nanocomposites.5,10,23,29,30 It indicates that the multimagnetic core structure is beneficial for a high magnetic property of the nanocomposites. The absorption spectrum of the nanocomposites is shown in Figure S2. It exhibits not only a broad absorption peak of Fe3O4 but also a narrow absorption peak (centered at ∼970 nm) originating from Yb3+ ions. Under the excitation of a 980 nm laser diode, the upconversion luminescence spectrum of the Fe3O4/NaYF4: Yb, Er nanocomposites was recorded and shown in Figure 3b. Three emission peaks centered at ∼520, 546 (green), and 655 nm (red) were observed. They were attributed to the 2 H1/2−4I15/2, 4S3/2−4I15/2, and 4F9/2−4I15/2 electronic transitions of Er3+ ions, respectively, which were populated to the excited states mainly via energy transfer from Yb3+ ions. The superparamagnetic and upconversion luminescent properties of the Fe3O4/NaYF4: Yb, Er nanocomposites are visualized in Figure 3c. Under the assistance of a commercial magnet, the nanocomposites can be concentrated rapidly (within 15 s), indicating the fast magnetic responsiveness of the nanocomposites. The concentrated nanocomposites can also be redispersed easily when the magnet is removed. Under the excitation of a commercial continuous-wave 980 nm laser diode, intense green emission can be observed. These unique properties render the nanocomposites promising in the magnetically targeted upconversion bioimaging applications.

Figure 4. FTIR spectrum of the Fe3O4/NaYF4: Yb, Er nanocomposites.

1635, and 1125 cm−1 were observed. They are attributed to the stretching vibrations of N−H, bending vibrations of N−H, and stretching vibrations of C−N, respectively, indicating the coating of the nanocomposites by the polyelectrolyte. It was further confirmed by the positive zeta potential of the nanocomposites dispersed in water, which was determined to be 40.2 mV. Zeta potential is also an important indication of the colloidal stability. Such a large zeta potential (greater than 30 mV) indicates a stable colloidal system of the nanocomposites that is absence of agglomeration.44−46 Therefore, the PEI-capped magnetic and upconversion luminescent nanocomposites hold great potential in bioimaging applications. Cytotoxicity of the Fe3O4/NaYF4: Yb, Er Nanocomposites. Prior to the bioimaging experiments, the cytotoxicity of the Fe3O4/NaYF4: Yb, Er nanocomposites on two different cell lines, namely, human breast cancer MCF-7 cells and mouse fibroblast 3T3 cells, was evaluated by the standard MTT method. It can be seen from Figure 5 that the cytotoxicity of the Fe3O4/NaYF4: Yb, Er nanocomposites on MCF-7 cells was 148

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during the incubation process, suggesting negligible cytotoxicity of the Fe3O4/NaYF4: Yb, Er nanocomposites induced by the magnetic field, it would be very meaningful if we can reduce the dosage of the nanocomposites in their biomedical applications by exerting an external magnetic field. Cell Imaging of the Fe3O4/NaYF4: Yb, Er Nanocomposites. The confocal images of MCF-7 cells incubated with different concentrations of the Fe3O4/NaYF4: Yb, Er nanocomposites with or without external magnetic field were presented in Figure 6. It was found that a relatively high concentration (200 μg/mL) of the Fe3O4/NaYF4: Yb, Er nanocomposites was needed to obtain clear upconversion luminescence images without external magnetic field (Figure 6a), while a rather low concentration (5 μg/mL) of the nanocomposites was sufficient to acquire images with comparable quality under an external magnetic field (Figure 6b). Little upconversion luminescence could be observed with the same concentration of the nanocomposites without external magnetic field (Figure 6c). Similar results were obtained with 3T3 cells (Figure S4). It indicates that the sensitivity of the cell imaging can be improved significantly by the magnetic enrichment function of the nanocomposites. Moreover, the dosage of the nanocomposites necessary for cell imaging can be decreased significantly under the magnetic field. As the decrease in the dosage of the nanocomposites suggests a lower cytotoxicity of the nanocomposites on the cells, and the nanocomposites exhibited tolerable cytotoxicity to both cell lines with the concentration of 5 μg/mL (cell viability: ∼90% or higher), sensitive and low-toxic cell imaging can be realized with the magnetic upconversion luminescent nanocomposites

Figure 5. Cytotoxicity of the Fe3O4/NaYF4: Yb, Er nanocomposites on MCF-7 cells with or without external magnetic field during the incubation process.

concentration-dependent. The viability of MCF-7 cells was ∼90% when incubating with 5 μg/mL of the Fe3O4/NaYF4: Yb, Er nanocomposites for 24 h. It decreased gradually to ∼61%, as the concentration of the nanocomposites increased to 500 μg/ mL. The concentration-dependent cytotoxicity of the nanocomposites on 3T3 cells was also observed (Figure S3). The moderate cytotoxicity of the nanocomposites under high dosages was probably induced by the PEI polycation capped on the surface of the nanocomposites in a necrotic manner, with the cell membrane damaged first and then the organelles.47−49 Because only slight changes in the cell viability were observed when an external magnetic field was applied

Figure 6. (a) Confocal images of MCF-7 cells incubated with 200 μg/mL of the Fe3O4/NaYF4: Yb, Er nanocomposites without external magnetic field. Confocal images of MCF-7 cells incubated with 5 μg/mL of the Fe3O4/NaYF4: Yb, Er nanocomposites (b) with or (c) without external magnetic field. 149

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as imaging agents under the assistance of an external magnetic field.



ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsanm.7b00059. XPS pattern and absorption spectrum of the Fe3O4/ NaYF4: Yb, Er nanocomposites. Cytotoxicity of the nanocomposites on mouse fibroblast 3T3 cells. Confocal images of 3T3 cells incubated with the nanocomposites (PDF)



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SUMMARY AND CONCLUSIONS In summary, water-dispersible multimagnetic-beads-embedded Fe3O4/NaYF4: Yb, Er nanocomposites with an average diameter of ∼33.8 nm were fabricated with polyelectrolytecapped Fe3O4 magnetic beads serving as the seeds. The multiple magnetic beads embedded in the Fe3O4/NaYF4: Yb, Er nanocomposites endow the nanocomposites super-paramagnetic property with a high saturation magnetization of 17.8 emu/g, while NaYF4:Yb, Er endows the nanocomposites upconversion luminescence under the excitation of a 980 nm laser diode. Although moderate cytotoxicity of the Fe3O4/ NaYF4: Yb, Er nanocomposites was observed for human breast cancer MCF-7 cells and mouse fibroblast 3T3 cells with a high concentration of the nanocomposites, which might be induced by the capping PEI, sensitive and low-toxic upconversion luminescence imaging of the cells was realized by decreasing significantly the dosage of the nanocomposites under the assistance of an external magnetic field. By anchoring specific targeting molecules and drugs (such as chemotherapeutic, photodynamic, and photothermal agents) on the surface of the nanocomposites, they shall hold great potential for magnetic/ molecule targeted labeling, magnetic resonance/upconversion luminescence bimodal bioimaging, drug delivery, therapies, and so on.



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AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected]. *E-mail: [email protected]. ORCID

Xia Hong: 0000-0002-8166-6562 Author Contributions

The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript. Notes

The authors declare no competing financial interest.



ACKNOWLEDGMENTS This work was supported by the National Natural Science Foundation of China (Grant Nos. 51272040 and 11604043), Thirteenth Five-Year Science and Technology Research Project of Education Department of Jilin Province (No. JJKH20170910KJ), the 111 project (No. B13013), and project funded by China Postdoctoral Science Foundation (No. 2017M611294). 150

DOI: 10.1021/acsanm.7b00059 ACS Appl. Nano Mater. 2018, 1, 145−151

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DOI: 10.1021/acsanm.7b00059 ACS Appl. Nano Mater. 2018, 1, 145−151