Research ArticleBasic Science Investigations

RGD Peptide–Conjugated Multimodal NaGdF4:Yb3+/Er3+ Nanophosphors for Upconversion Luminescence, MR, and PET Imaging of Tumor Angiogenesis

Junghan Lee, Tae Sup Lee, Jiyoung Ryu, Sukmin Hong, Moonsik Kang, Kangbin Im, Joo Hyun Kang, Sang Moo Lim, Sun Park and Rita Song
Journal of Nuclear Medicine January 2013, 54 (1) 96-103; DOI: https://doi.org/10.2967/jnumed.112.108043

Article Figures & Data

Figures

  • FIGURE 1.
    FIGURE 1.

    Synthesis scheme of 124I-(cRGDyk)2-UCNP conjugates. Polymer-coated UCNP (pcUCNP) was reacted both with (cRGDyk)2 peptide and with MeO-PEG-NH2 (molecular weight, 2,000) using EDC/N-hydroxysulfosuccinimide. Tyrosine residue of (cRGDyk)2 was labeled with 124I using Iodo-Beads (Pierce).

  • FIGURE 2.
    FIGURE 2.

    (A) TEM bright-field image. (B) High-resolution TEM image of NaGdF4:Yb3+/Er3+ and selected area electron diffraction pattern (inset). (C) Emission spectra (green) and ultraviolet–visible spectra (black) of NaGdF4:Yb3+/Er3+ and upconversion luminescence of UCNP in toluene under excitation of 980-nm laser (inset). a.u. = arbitrary units.

  • FIGURE 3.
    FIGURE 3.

    (A) Gel electrophoresis image of (cRGDyk)2-UCNP conjugates with various ratios of PEG to peptide: lane a, polymer-coated UCNP; lane b, (cRGDyk)2-UCNP without PEG (UCNP:(cRGDyk)2 = 1:1,000); lanes c, d, and e, UCNP:(cRGDyk)2:PEG = 1:800:200, 1:500:500, and 1:200:800, respectively; lane f, pegylated UCNP without (cRGDyk)2 (UCNP:PEG = 1:1,000). Gel condition: 1% agarose gel, 0.5× TBE buffer (pH 8.5), 50 V⋅cm−1, 40 min. Gel image was obtained by SYBR green (Invitrogen) staining. (B) Stability of nanoparticles incubated in 1× phosphate-buffered saline for 24 h at room temperature. (C) Hydrodynamic size of UCNPs measured by dynamic light scattering (polymer-coated UCNP [pcUCNP], 30 ± 8 nm [black]; (cRGDyk)2-UCNP [UCNP:(cRGDyk)2:PEG = 1:200:800], 32 ± 9 nm) [red]).

  • FIGURE 4.
    FIGURE 4.

    Upconversion luminescence image of U87MG cells and cytotoxicity test. (A) Image of U87MG cells incubated with (cRGDyk)2-UCNP. (B) Image of U87MG cells incubated with (cRGDyk)2-UCNP after pretreatment with excess of (cRGDyk)2 peptide. (C) Methylthiazol-tetrazolium assay cell proliferation assay.

  • FIGURE 5.
    FIGURE 5.

    (A) Time-dependent signal-to-noise ratio (SNR) change in 124I-(cRGDyk)2-UCNPs with or without blocking dose of (cRGDyk)2 peptide. (B) Time-dependent %ID/g change in 124I-(cRGDyk)2-UCNPs with or without blocking dose of (cRGDyk)2 peptide. A. U. = 5 arbitrary units.

  • FIGURE 6.
    FIGURE 6.

    Biologic TEM images of U87MG tumor tissues. (A) Tumor tissue injected with 124I-(cRGDyk)2-UCNPs (1.66 MBq/2 mg). (B) Tumor tissue injected with 124I-(cRGDyk)2-UCNP (1.66 MBq/2 mg) after blocking with excess amount of (cRGDyk)2 peptide (10 mg/kg). Frozen tumor section (1-μm thickness) was stained with 3% uranyl acetate for 20 min and lead citrate for 15 min. Arrow: UCNPs.

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