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SCIENCE CHINA Chemistry, Volume 60, Issue 9: 1219-1229(2017) https://doi.org/10.1007/s11426-017-9088-x

Synthesis of different-sized gold nanostars for Raman bioimaging and photothermal therapy in cancer nanotheranostics

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  • ReceivedApr 10, 2017
  • AcceptedMay 23, 2017
  • PublishedJul 28, 2017

Abstract

Gold nanoparticles (AuNPs) have been attractive for nanomedicine because of their pronounced optical properties. Here, we customerized the methods to synthesize two types of gold nanostars, Au nanostars-1 and Au nanostars-2, which have different spire lengths and optical properties, and also spherical AuNPs. Compared to nanospheres, gold nanostars were less toxic to a variety of cells, including macrophages. Au nanostars-1 and Au nanostars-2 also manifested a similar pattern of tissue distribution upon in vivo administration in mice to that of nanospheres, and but reveled less liver retention than nanospheres. Due to their strong absorption in the near-infrared (NIR), Au nanostars-2 induced a strong hyperthermia effect in vitro upon excitation at 808 nm, and elicited a robust photothermal therapy (PTT) efficacy in ablating tumors in a mouse model of orthotopic breast cancer using 4T1 breast cancer cells. Meanwhile, Au nanostars-1 showed a great capability to enhance the Raman signal through surface-enhanced Raman spectroscopy (SERS) in 4T1 cells. Our combined results opened a new avenue to develop Au nanostars for cancer imaging and therapy.


Funded by

National Basic Research Program(2014CB932000)

Strategic Priority Research Program of the Chinese Academy of Sciences(XDB14000000)

National Natural Science Foundation of China(21425731,21637004)


Acknowledgment

This work was supported by the National Basic Research Program (2014CB932000), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB14000000) and the National Natural Science Foundation of China (21425731, 21637004).


Interest statement

The authors declare that they have no conflict of interest.


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  • Figure 1

    Physical characterization of AuNPs. (a) TEM images of Au nanostars-1, Au nanostars-2 and Au nanospheres; (b) hydrodynamic diameters of AuNPs measured by DLS; (c) zeta-potentials of AuNPs solutions; (d) UV-Vis spectra of Au nanostars-1, Au nanostars-2 and Au nanospheres in water (color online).

  • Figure 2

    Cytotoxicity evaluation upon AuNPs in J774A.1 cells. (a) Cell viability determined by the MTT assay in J774A.1 cells upon exposure to AuNPs at 1, 10 and 20 μg/mL for 24 h (n=6); (b) relative LDH release in J774A.1 cells treated with AuNPs for 24 h (n=6); (c) cellular energy metabolism in J774A.1 cells, as characterized by ATP production, in response to AuNPs for 24 h. Cellular ATP mass was assayed by the bioluminescent intensity on a microplate reader and relative ATP levels were quantified by normalizing to the untreated control (n=6) (color online).

  • Figure 3

    Cytotoxicity determination in 4T1 cells responded to AuNPs. (a) Cytotoxicity determined by the MTT assay in 4T1 cells treated with AuNPs at concentrations of 1, 10 and 20 μg/mL for 24 h (n=6); (b) ATP production in 4T1 cells upon AuNPs for 24 h (n=6); (c) ATP production levels quantified after cells were treated with AuNPs at various concentrations for 24 h (n=6). Arrows represent the drop, compared to untreated control: one arrow, 20% reduction; two arrows, ~40% reduction; three arrows, ~60% reduction (color online).

  • Figure 4

    Cellular uptake and the localization of AuNPs. (a) Quantification of the amount of elemental Au in cells by ICP-MS in J774.1A cells after 24-h incubation with 10 μg/mL AuNPs (n=6); (b) TEM images of J774.1A cells post treatment with AuNPs. After incubation with 10 μg/mL Au nanostars-1 and Au nanospheres for 24 h, cells were collected for TEM analysis of intracellular AuNPs. Blue arrows denote nanoparticles, and red arrows indicate phagosomes (color online).

  • Figure 5

    Biodistrbution and histological examinations of tissues upon AuNPs in vivo. (a) Biodistribution of AuNPs in various organs in mice after AuNPs administration at 10 μg/mouse for 24 h. (b) H&E staining of various tissues from mice administrated with AuNPs at 10 μg/mice for 24 h. Original magnification, ×100 (color online).

  • Figure 6

    The photothermal effect of Au nanostars-1 in vitro. (a) The photothermal effect curve of the temperature of an Au nanostars-1 solution in water under NIR irradiation for 10 min; (b) cytotoxicity of 4T1 cells at the different concentrations of Au nanostars-1 with or without NIR determined by the MTT assay (n=6) (color online).

  • Figure 7

    Hyperthermia effect and photothermal ablation of tumors in mice. (a) Laser irradiation temperature elevation in 4T1 tumors implanted in mice after injection of nanostars-1. The temperature was recorded at different time intervals after material injection. (b) The tumor growth curves in mice upon PTT with nanostars-1 over the time course (n=3). (c) The alterations of body weight of mice upon PTT with nanostars-1 over time (n=3). (d) The representative images of tumors post PTT at different time times post injection (color online).

  • Figure 8

    Raman spectra of nanostars-1 in 4T1 cells. (a) Raman spectra of Au nanostars-1 and Au nanospheres incubated with 4-MBA overnight; (b, c) a representative Raman bright-field image of a 4T1 cell after exposure to with nanostars-1-MBA for 24 h was selected for streamline mapping and the corresponding Raman spectra. Points 1‒4 indicated different locations inside or outside of the selected cell (color online).

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