Research ArticleMATERIALS SCIENCE

General and programmable synthesis of hybrid liposome/metal nanoparticles

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Science Advances  16 Dec 2016:
Vol. 2, no. 12, e1601838
DOI: 10.1126/sciadv.1601838
  • Fig. 1 Programmable and facile synthesis of various liposome/metal hybrid nanoparticles.

    (A and B) Schematic illustration of selective encoding of a reducing agent in a liposome [step 1 (A)] and spontaneous crystallization of metal precursors into metal nanoparticles inside the liposome through the diffusion of the metal precursors [step 2 (B)]. Bottom two photos correspond to the photographs of the resulting hybrid solutions and representative TEM images for the as-made hybrid particles. Scale bars, 50 nm.

  • Fig. 2 Self-crystallization of GNP in a reducing agent–encoded (LGNP).

    (A and B) Representative TEM images of liposomes (A) and resulting LGNP (B) according to filter pore size (30, 50, 100, and 200 nm). (C and D) Size distributions (C) and relation (D) between the liposomes and the LGNP. (E) Representative absorbance spectra of the LGNP solutions with different sizes. a.u., arbitrary units. (F) Plot of absorbance at SPR peak (541 nm) of the LGNP as a function of time. (G and H) Representative TEM image (G) and EDS spectrum (H) of the LGNP prepared by using ascorbic acid as another reducing agent. (I) Concentrations of gold precursor in the liposome due to diffusion after 0, 80, and 160 μs. (J) The number of gold atoms in the liposome due to reduction after 0, 20, and 40 hours. (K) Concentration of gold precursor (black) and the number of gold atoms (red) inside the liposome as a function of time. Scale bars, 50 nm (A, B, and G) and 10 nm [insets in (B), (G′), (I), and (J)].

  • Fig. 3 Extension of our proposed programmable synthesis to the selective synthesis of a wide variety of liposome/metal hybrids.

    (A to C) Representative TEM images of liposome/monometallic hybrids [Ag (A), Pd (B), and Pt (C)]. (D to F) Representative TEM images of liposome/bimetallic hybrids [Au-Ag (D), Au-Pd (E), and Au-Pt (F)]. (G to I) Representative TEM images and corresponding EDS element maps of the liposome/bimetallic hybrids [Au-Ag (G), Au-Pd (H), and Au-Pt (I)]. (J to L) Representative CS-TEM images, lattice-resolved images (numbered boxes), and electron diffraction patterns (the insets of the numbered boxes) of liposome/bimetallic hybrids [Au-Ag (J), Au-Pd (K), and Au-Pt (L)]. (M and N) Atomic percentages (M) and absorbance spectra (N) of liposome/Au-Pt hybrids synthesized from the precursor molar ratios of 2:1 (Au/Pt), 1:1, and 1:2. Scale bars, 50 nm (A to F and J to L), 20 nm (A′ to F′, and G to I), and 2 nm [numbered boxes in (J), (K), and (L)].

  • Fig. 4 Analysis of endocytosis efficiency of LGNP and intracellular imaging via SERS.

    (A) Schematic representation for cellular uptake of LGNP and GNP. (B) Comparison of endocytosis efficiency using U-87 MG cells with a confocal microscope. First row: Differential interference contrast image; second row: scattering image; third row: overlay image. First column: Cells only; second column: LGNP; third column: GNP. (C) Mean signal intensity per single cell from control (cells only) (7.2 ± 1.8), GNP (125.9 ± 41.3), and LGNP (1374.8 ± 141.6). (D) 3D analysis of the intracellular distribution of LGNP in the single cell. (E and F) Optical microscope images and Raman maps obtained from U-87 MG, MDA-MB-231, and HEK 293T/17 cells after being treated with LGNP (E) and GNP (F). Scale bars, 10 μm (B and D to F).

Supplementary Materials

  • Supplementary material for this article is available at http://advances.sciencemag.org/cgi/content/full/2/12/e1601838/DC1

    Simulation details

    fig. S1. Schematic illustration of conventional approaches for liposome/metal hybrids and their critical limitations.

    fig. S2. Additional TEM images of LGNP (using membrane filter with a pore diameter of 100 nm).

    fig. S3. Photographs and absorbance spectra of control experiments.

    fig. S4. Reduction of gold ions above the transition temperature of lipid (DSPC).

    fig. S5. Molecular structure of DSPC and EDS spectrum and relative atomic percentages of as-prepared liposome/Au and liposome/Ag hybrid nanoparticles.

    fig. S6. Time-dependent representative absorbance spectra of programmable liposome solution after the exposure with gold precursor.

    fig. S7. Diffusivities of acetamide and neutral gold ion complex.

    fig. S8. Photographs and absorbance spectra of solutions of the gold precursor–encoded liposome after addition of reducing agent.

    fig. S9. Additional TEM images of various liposome/metal hybrid nanoparticles.

    fig. S10. Representative time-resolved absorbance spectra of liposome/monometallic hybrid nanoparticle.

    fig. S11. Size distributions of liposome/monometallic and liposome/bimetallic hybrids.

    fig. S12. EDS spectra of liposome/bimetallic hybrids.

    fig. S13. Representative TEM images and corresponding EDS elemental line profiles of liposome/bimetallic hybrids.

    fig. S14. Representative TEM images of liposome/bimetallic hybrids synthesized from different precursor molar ratios.

    fig. S15. Atomic percentages and absorbance spectra of liposome/Au-Ag hybrids and liposome/Au-Pd hybrids synthesized from different precursor molar ratios.

    fig. S16. Representative relative absorbance at the SPR peaks of LGNP, GNP, and GNR under a wide variety of biologically relevant solutions and representative relative absorbance of LGNP with time duration of up to 1 month.

    fig. S17. Viability of U-87 MG cells treated with LGNP and GNP solutions.

    fig. S18. Optical microscope images and Raman spectra obtained from various cells after being treated with LGNP and GNP.

    fig. S19. Fluorescent image and Raman spectra obtained from Alexa Fluor 546–stained U-87 MG cells, and optical microscope images and Raman maps obtained from Alexa Fluor 546–stained U-87MG cells after being treated with LGNP and GNP.

    table S1. Calculated relative atomic percentages of gold and oxygen atoms in LGNP.

    table S2. The number of metal atoms per unit volume in liposome/Au, liposome/Ag, and liposome/Pd hybrids, measured by inductively coupled plasma atomic emission spectroscopy.

    Reference (51)

  • Supplementary Materials

    This PDF file includes:

    • Simulation details
    • fig. S1. Schematic illustration of conventional approaches for liposome/metal hybrids and their critical limitations.
    • fig. S2. Additional TEM images of LGNP (using membrane filter with a pore diameter of 100 nm).
    • fig. S3. Photographs and absorbance spectra of control experiments.
    • fig. S4. Reduction of gold ions above the transition temperature of lipid (DSPC).
    • fig. S5. Molecular structure of DSPC and EDS spectrum and relative atomic percentages of as-prepared liposome/Au and liposome/Ag hybrid nanoparticles.
    • fig. S6. Time-dependent representative absorbance spectra of programmable liposome solution after the exposure with gold precursor.
    • fig. S7. Diffusivities of acetamide and neutral gold ion complex.
    • fig. S8. Photographs and absorbance spectra of solutions of the gold precursor–encoded liposome after addition of reducing agent.
    • fig. S9. Additional TEM images of various liposome/metal hybrid nanoparticles.
    • fig. S10. Representative time-resolved absorbance spectra of liposome/monometallic hybrid nanoparticle.
    • fig. S11. Size distributions of liposome/monometallic and liposome/bimetallic hybrids.
    • fig. S12. EDS spectra of liposome/bimetallic hybrids.
    • fig. S13. Representative TEM images and corresponding EDS elemental line profiles of liposome/bimetallic hybrids.
    • fig. S14. Representative TEM images of liposome/bimetallic hybrids synthesized from different precursor molar ratios.
    • fig. S15. Atomic percentages and absorbance spectra of liposome/Au-Ag hybrids and liposome/Au-Pd hybrids synthesized from different precursor molar ratios.
    • fig. S16. Representative relative absorbance at the SPR peaks of LGNP, GNP, and GNR under a wide variety of biologically relevant solutions and representative relative absorbance of LGNP with time duration of up to 1 month.
    • fig. S17. Viability of U-87 MG cells treated with LGNP and GNP solutions.
    • fig. S18. Optical microscope images and Raman spectra obtained from various cells after being treated with LGNP and GNP.
    • fig. S19. Fluorescent image and Raman spectra obtained from Alexa Fluor 546–stained U-87 MG cells, and optical microscope images and Raman maps obtained from Alexa Fluor 546–stained U-87MG cells after being treated with LGNP and GNP.
    • table S1. Calculated relative atomic percentages of gold and oxygen atoms in LGNP.
    • table S2. The number of metal atoms per unit volume in liposome/Au, liposome/Ag, and liposome/Pd hybrids, measured by inductively coupled plasma atomic emission spectroscopy.
    • Reference (51)

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