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Synthesis, Characterization, and Application of Core-Shell Co0.16Fe2.84O4@NaYF4(Yb, Er) and Fe3O4@NaYF4(Yb, Tm) Nanoparticle as Trimodal (MRI, PET/SPECT, and Optical) Imaging Agents.

Cui X, Mathe D, Kovács N, Horváth I, Jauregui-Osoro M, Torres Martin de Rosales R, Mullen GE, Wong W, Yan Y, Krüger D, Khlobystov AN, Gimenez-Lopez M, Semjeni M, Szigeti K, Veres DS, Lu H, Hernández I, Gillin WP, Protti A, Petik KK, Green MA, Blower PJ - Bioconjug. Chem. (2015)

Bottom Line: They comprise Fe3O4@NaYF4 core/shell nanoparticles (NPs) with different cation dopants in the shell or core, including Co0.16Fe2.84O4@NaYF4(Yb, Er) and Fe3O4@NaYF4(Yb, Tm).These NPs are stabilized by bisphosphonate polyethylene glycol conjugates (BP-PEG), and then show a high transverse relaxivity (r2) up to 326 mM(-1) s(-1) at 3T, a high affinity to [(18)F]-fluoride or radiometal-bisphosphonate conjugates (e.g., (64)Cu and (99m)Tc), and fluorescent emissions from 500 to 800 nm under excitation at 980 nm.Preliminary results in sentinel lymph node imaging in mice indicate the advantages of multimodal imaging.

View Article: PubMed Central - PubMed

Affiliation: King's College London , Division of Imaging Sciences and Biomedical Engineering, Fourth Floor Lambeth Wing, St. Thomas Hospital, London, SE1 7EH, United Kingdom.

ABSTRACT
Multimodal nanoparticulate materials are described, offering magnetic, radionuclide, and fluorescent imaging capabilities to exploit the complementary advantages of magnetic resonance imaging (MRI), positron emission tomography/single-photon emission commuted tomography (PET/SPECT), and optical imaging. They comprise Fe3O4@NaYF4 core/shell nanoparticles (NPs) with different cation dopants in the shell or core, including Co0.16Fe2.84O4@NaYF4(Yb, Er) and Fe3O4@NaYF4(Yb, Tm). These NPs are stabilized by bisphosphonate polyethylene glycol conjugates (BP-PEG), and then show a high transverse relaxivity (r2) up to 326 mM(-1) s(-1) at 3T, a high affinity to [(18)F]-fluoride or radiometal-bisphosphonate conjugates (e.g., (64)Cu and (99m)Tc), and fluorescent emissions from 500 to 800 nm under excitation at 980 nm. The biodistribution of intravenously administered particles determined by PET/MR imaging suggests that negatively charged Co0.16Fe2.84O4@NaYF4(Yb, Er)-BP-PEG (10K) NPs cleared from the blood pool more slowly than positively charged NPs Fe3O4@NaYF4(Yb, Tm)-BP-PEG (2K). Preliminary results in sentinel lymph node imaging in mice indicate the advantages of multimodal imaging.

No MeSH data available.


Related in: MedlinePlus

HRTEM studies of NPs: (a) HRTEM images of Fe3O4@NaYF4(Yb, Tm); (b) fast Fourier transformof the selectedarea in part a, showing two sets of diffraction patterns. The diffractionpattern marked in blue belonged to cubic Fe3O4, and the one marked in red was assigned as cubic NaYF4; (c) high angle annular dark field image of Fe3O4@NaYF4(Yb, Tm), showing the Z contrastdifference between the shell and core of particles induced by a slightlyhigher average atomic number in the shell after doping with heavyatoms Yb and Tm; (d) HRTEM image revealed the core–shell structureof NP Co0.16Fe2.84O4@NaYF4(Yb, Er). Atomic lattice fringes 2.97 and 4.14 Å correspondedto (022) and (200) planes of Fe3O4, respectively.The inset is a fast Fourier transform of the micrograph.
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fig2: HRTEM studies of NPs: (a) HRTEM images of Fe3O4@NaYF4(Yb, Tm); (b) fast Fourier transformof the selectedarea in part a, showing two sets of diffraction patterns. The diffractionpattern marked in blue belonged to cubic Fe3O4, and the one marked in red was assigned as cubic NaYF4; (c) high angle annular dark field image of Fe3O4@NaYF4(Yb, Tm), showing the Z contrastdifference between the shell and core of particles induced by a slightlyhigher average atomic number in the shell after doping with heavyatoms Yb and Tm; (d) HRTEM image revealed the core–shell structureof NP Co0.16Fe2.84O4@NaYF4(Yb, Er). Atomic lattice fringes 2.97 and 4.14 Å correspondedto (022) and (200) planes of Fe3O4, respectively.The inset is a fast Fourier transform of the micrograph.

Mentions: Fe3O4@NaYF4 core/shellNPs were synthesized by a two-step thermolysis approach using ironpentacarbonyl and trifluoroacetate salts (Scheme S1 in Supporting Information). Lanthanide cations (Yb,Er, or Tm) were doped into the NaYF4 shell for the purposeof up-conversion fluorescence, and Co was doped into the Fe3O4 core to adjust the magnetic property of NPs. Transmissionelectron microscope (TEM) images (Figure 1) revealed that the NPs with different dopingshared a similar size and morphology. X-ray powder diffraction (XRD)patterns implied that these Fe3O4@NaYF4 core/shell NPs consisted of two distinct phases, Fe3O4 and α-NaYF4 (FigureS1). High resolution transmission electron micrograph (HRTEM)studies of NPs Fe3O4@NaYF4(Yb, Tm)showed atomic lattice fringes of 2.97 Å associated with the (022)and (202) planes of cubic Fe3O4 and 1.72 and2.94 Å corresponding to the (022) and (200) planes of cubic NaYF4, respectively (Figure 2a). The angle between the (022) and (202) planes was calculatedas 60°, consistent with the value measured on the HRTEM image.The electron diffraction patterns were obtained by the fast Fouriertransform analysis of the HRTEM image. Two sets of diffraction patternsfor Fe3O4 and NaYF4 were obtained,and each spot was assigned as indicated in Figure 2b. Analysis of the electron diffraction patternsindicated that core–shell structures were formed by growingthe (011̅) plane of NaYF4 on the (111̅) planeof Fe3O4 with a rotation angle of 30°.High angle annular dark field (HAADF, or Z contrast)imaging was employed to investigate the structure of NP Fe3O4@NaYF4(Yb, Tm), as its contrast was stronglydependent on average atomic number of the specimen but insensitiveto its thickness. The HAADF image of Fe3O4@NaYF4(Yb, Tm) NPs in Figure 2c clearly showed a core/shell structure, in which the Yb-and Tm-codoped NaYF4 shells appeared brighter than theFe3O4 cores. The core–shell structureof Fe3O4@NaYF4 NPs was also investigatedby bright field HRTEM. For instance, the HRTEM image of Co0.16Fe2.84O4@NaYF4(Yb, Er) NPs in Figure 2d showed a distinctcontrast difference between the Co-doped Fe3O4 core and the Yb/Er codoped NaYF4 shell, while the electrondiffraction pattern indicated the crystalline nature of the core.Despite the presence of heavy atoms Yb and Er, the shell appearedbrighter on bright field TEM image, since the contrast is determinedby the thickness and crystallinity of the specimen, as well as itselemental composition. The atomic lattice fringes of 2.97 and 4.14Å were associated with (022) and (200) planes, respectively,of the cubic Fe3O4 phase. The doping of Co intothe Fe3O4 lattice, and of Yb and Er into NaYF4 lattice, was confirmed by energy dispersive X-ray spectroscopy(EDX) (Figure S2). Compositional studieson Co/Yb/Er doped NPs were also carried out by X-ray photoelectronspectroscopy (XPS) and inductively coupled plasma mass spectrometry(ICP-MS) (Figure S3, Tables S3 and S4).ICP-MS results indicated a formulation of Co0.16Fe2.84O4 for the core, and the unexpected low Co toFe ratio was probably due to an incomplete decomposition of Co(acac)2. The molar ratio of Y:Yb:Er was measured by ICP-MS as 79.3:18.6:2.1,consistent with the ratio of starting materials (Y2O3, Yb2O3, and Er2O3). By comparing the relative content of Fe, Co, Y, Yb, and Er obtainedby ICP-MS and XPS (Table S3), it was clearthat dramatically less Fe and Co was detected by the surface techniqueXPS, than by ICP-MS or EDX. This is consistent with the proposed core–shellstructure observed by TEM.


Synthesis, Characterization, and Application of Core-Shell Co0.16Fe2.84O4@NaYF4(Yb, Er) and Fe3O4@NaYF4(Yb, Tm) Nanoparticle as Trimodal (MRI, PET/SPECT, and Optical) Imaging Agents.

Cui X, Mathe D, Kovács N, Horváth I, Jauregui-Osoro M, Torres Martin de Rosales R, Mullen GE, Wong W, Yan Y, Krüger D, Khlobystov AN, Gimenez-Lopez M, Semjeni M, Szigeti K, Veres DS, Lu H, Hernández I, Gillin WP, Protti A, Petik KK, Green MA, Blower PJ - Bioconjug. Chem. (2015)

HRTEM studies of NPs: (a) HRTEM images of Fe3O4@NaYF4(Yb, Tm); (b) fast Fourier transformof the selectedarea in part a, showing two sets of diffraction patterns. The diffractionpattern marked in blue belonged to cubic Fe3O4, and the one marked in red was assigned as cubic NaYF4; (c) high angle annular dark field image of Fe3O4@NaYF4(Yb, Tm), showing the Z contrastdifference between the shell and core of particles induced by a slightlyhigher average atomic number in the shell after doping with heavyatoms Yb and Tm; (d) HRTEM image revealed the core–shell structureof NP Co0.16Fe2.84O4@NaYF4(Yb, Er). Atomic lattice fringes 2.97 and 4.14 Å correspondedto (022) and (200) planes of Fe3O4, respectively.The inset is a fast Fourier transform of the micrograph.
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fig2: HRTEM studies of NPs: (a) HRTEM images of Fe3O4@NaYF4(Yb, Tm); (b) fast Fourier transformof the selectedarea in part a, showing two sets of diffraction patterns. The diffractionpattern marked in blue belonged to cubic Fe3O4, and the one marked in red was assigned as cubic NaYF4; (c) high angle annular dark field image of Fe3O4@NaYF4(Yb, Tm), showing the Z contrastdifference between the shell and core of particles induced by a slightlyhigher average atomic number in the shell after doping with heavyatoms Yb and Tm; (d) HRTEM image revealed the core–shell structureof NP Co0.16Fe2.84O4@NaYF4(Yb, Er). Atomic lattice fringes 2.97 and 4.14 Å correspondedto (022) and (200) planes of Fe3O4, respectively.The inset is a fast Fourier transform of the micrograph.
Mentions: Fe3O4@NaYF4 core/shellNPs were synthesized by a two-step thermolysis approach using ironpentacarbonyl and trifluoroacetate salts (Scheme S1 in Supporting Information). Lanthanide cations (Yb,Er, or Tm) were doped into the NaYF4 shell for the purposeof up-conversion fluorescence, and Co was doped into the Fe3O4 core to adjust the magnetic property of NPs. Transmissionelectron microscope (TEM) images (Figure 1) revealed that the NPs with different dopingshared a similar size and morphology. X-ray powder diffraction (XRD)patterns implied that these Fe3O4@NaYF4 core/shell NPs consisted of two distinct phases, Fe3O4 and α-NaYF4 (FigureS1). High resolution transmission electron micrograph (HRTEM)studies of NPs Fe3O4@NaYF4(Yb, Tm)showed atomic lattice fringes of 2.97 Å associated with the (022)and (202) planes of cubic Fe3O4 and 1.72 and2.94 Å corresponding to the (022) and (200) planes of cubic NaYF4, respectively (Figure 2a). The angle between the (022) and (202) planes was calculatedas 60°, consistent with the value measured on the HRTEM image.The electron diffraction patterns were obtained by the fast Fouriertransform analysis of the HRTEM image. Two sets of diffraction patternsfor Fe3O4 and NaYF4 were obtained,and each spot was assigned as indicated in Figure 2b. Analysis of the electron diffraction patternsindicated that core–shell structures were formed by growingthe (011̅) plane of NaYF4 on the (111̅) planeof Fe3O4 with a rotation angle of 30°.High angle annular dark field (HAADF, or Z contrast)imaging was employed to investigate the structure of NP Fe3O4@NaYF4(Yb, Tm), as its contrast was stronglydependent on average atomic number of the specimen but insensitiveto its thickness. The HAADF image of Fe3O4@NaYF4(Yb, Tm) NPs in Figure 2c clearly showed a core/shell structure, in which the Yb-and Tm-codoped NaYF4 shells appeared brighter than theFe3O4 cores. The core–shell structureof Fe3O4@NaYF4 NPs was also investigatedby bright field HRTEM. For instance, the HRTEM image of Co0.16Fe2.84O4@NaYF4(Yb, Er) NPs in Figure 2d showed a distinctcontrast difference between the Co-doped Fe3O4 core and the Yb/Er codoped NaYF4 shell, while the electrondiffraction pattern indicated the crystalline nature of the core.Despite the presence of heavy atoms Yb and Er, the shell appearedbrighter on bright field TEM image, since the contrast is determinedby the thickness and crystallinity of the specimen, as well as itselemental composition. The atomic lattice fringes of 2.97 and 4.14Å were associated with (022) and (200) planes, respectively,of the cubic Fe3O4 phase. The doping of Co intothe Fe3O4 lattice, and of Yb and Er into NaYF4 lattice, was confirmed by energy dispersive X-ray spectroscopy(EDX) (Figure S2). Compositional studieson Co/Yb/Er doped NPs were also carried out by X-ray photoelectronspectroscopy (XPS) and inductively coupled plasma mass spectrometry(ICP-MS) (Figure S3, Tables S3 and S4).ICP-MS results indicated a formulation of Co0.16Fe2.84O4 for the core, and the unexpected low Co toFe ratio was probably due to an incomplete decomposition of Co(acac)2. The molar ratio of Y:Yb:Er was measured by ICP-MS as 79.3:18.6:2.1,consistent with the ratio of starting materials (Y2O3, Yb2O3, and Er2O3). By comparing the relative content of Fe, Co, Y, Yb, and Er obtainedby ICP-MS and XPS (Table S3), it was clearthat dramatically less Fe and Co was detected by the surface techniqueXPS, than by ICP-MS or EDX. This is consistent with the proposed core–shellstructure observed by TEM.

Bottom Line: They comprise Fe3O4@NaYF4 core/shell nanoparticles (NPs) with different cation dopants in the shell or core, including Co0.16Fe2.84O4@NaYF4(Yb, Er) and Fe3O4@NaYF4(Yb, Tm).These NPs are stabilized by bisphosphonate polyethylene glycol conjugates (BP-PEG), and then show a high transverse relaxivity (r2) up to 326 mM(-1) s(-1) at 3T, a high affinity to [(18)F]-fluoride or radiometal-bisphosphonate conjugates (e.g., (64)Cu and (99m)Tc), and fluorescent emissions from 500 to 800 nm under excitation at 980 nm.Preliminary results in sentinel lymph node imaging in mice indicate the advantages of multimodal imaging.

View Article: PubMed Central - PubMed

Affiliation: King's College London , Division of Imaging Sciences and Biomedical Engineering, Fourth Floor Lambeth Wing, St. Thomas Hospital, London, SE1 7EH, United Kingdom.

ABSTRACT
Multimodal nanoparticulate materials are described, offering magnetic, radionuclide, and fluorescent imaging capabilities to exploit the complementary advantages of magnetic resonance imaging (MRI), positron emission tomography/single-photon emission commuted tomography (PET/SPECT), and optical imaging. They comprise Fe3O4@NaYF4 core/shell nanoparticles (NPs) with different cation dopants in the shell or core, including Co0.16Fe2.84O4@NaYF4(Yb, Er) and Fe3O4@NaYF4(Yb, Tm). These NPs are stabilized by bisphosphonate polyethylene glycol conjugates (BP-PEG), and then show a high transverse relaxivity (r2) up to 326 mM(-1) s(-1) at 3T, a high affinity to [(18)F]-fluoride or radiometal-bisphosphonate conjugates (e.g., (64)Cu and (99m)Tc), and fluorescent emissions from 500 to 800 nm under excitation at 980 nm. The biodistribution of intravenously administered particles determined by PET/MR imaging suggests that negatively charged Co0.16Fe2.84O4@NaYF4(Yb, Er)-BP-PEG (10K) NPs cleared from the blood pool more slowly than positively charged NPs Fe3O4@NaYF4(Yb, Tm)-BP-PEG (2K). Preliminary results in sentinel lymph node imaging in mice indicate the advantages of multimodal imaging.

No MeSH data available.


Related in: MedlinePlus