Research ArticleHEALTH AND MEDICINE

Mass spectrometry imaging of the in situ drug release from nanocarriers

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Science Advances  31 Oct 2018:
Vol. 4, no. 10, eaat9039
DOI: 10.1126/sciadv.aat9039
  • Fig. 1 MS characterization of MoS2 nanosheets.

    (A to C) LDI mass spectra of (A) bare MoS2 nanosheets, (B) PEG-MoS2 nanosheets, and (C) DOX/PEG-MoS2 nanosheets. (D) Calibration curve plotted average ion intensity ratio of DOX (m/z = 321.0) to MoS2 nanosheets (m/z = 193.8) versus DOX loading ratio ([DOX]/[MoS2 nanosheets]). The calibration curve was obtained by spiking DOX/PEG-MoS2 nanosheets with a gradient drug/carrier ratio into a liver tissue homogenate. The fingerprint ion signals of mass spectra peaks are assigned as follows: m/z = 140.9 to 148.9, [MoO3]; m/z = 155.9 to 163.9, [MoO4]; m/z = 171.8 to 179.8, [MoS2O]; m/z = 187.8 to 195.8, [MoS2O2]; m/z = 203.8 to 211.8, [MoS2O3]; and m/z = 219.8 to 227.8, [MoS2O4]. a.u., arbitrary units.

  • Fig. 2 Distribution of bare MoS2 nanosheets in the liver of orthotopic H22 tumor model mice after 24-hour intravenous injection.

    (A and B) H&E-stained images of the (A) tumor-bearing liver tissue and (B) zoomed-in area of interest. (C and D) Corresponding LDI MSI images showing the distribution of bare MoS2 nanosheets in (C) tumor-bearing liver tissue and (D) the corresponding zoomed-in area. (E) Average ion intensity of bare MoS2 nanosheets in normal tissue and tumor foci. (F) Average ion intensity ratio of MoS2 in normal tissue and tumor foci after 24- and 48-hour intravenous injection, respectively. Ten regions of interest (50 pixels each) were selected in both normal tissue and tumor foci. ***P < 0.01. n.s., no significant difference.

  • Fig. 3 Biodistribution and drug release studies of DOX/PEG-MoS2 revealed by LDI MSI.

    (A and B) Images of the biodistribution of DOX/PEG-MoS2 nanosheets in tissues of (A) H22 and (B) 4T1 tumor model mice. (C and D) Average drug/carrier ratio in tissues of (C) H22 tumor and (D) 4T1 tumor models. The average drug/carrier ratios in each organ of (C) and (D) were obtained on the basis of the calibration curve in Fig. 1D, by calculating the average ion intensity ratio of DOX (m/z = 321.0) over MoS2 nanosheets (m/z = 193.8) in three randomly selected regions of corresponding organ (250 pixels each) in H22 and 4T1 tumor model mice, respectively. Scale bars, 5 mm. The statistical results shown in this figure were obtained from the mice that we show here, but we have tested three different mice in each group, and they all showed similar results.

  • Fig. 4 Images of the distribution of MoS2 nanosheets and their payload anticancer drug DOX in the liver tissue of orthotopic H22 tumor model mice after 24-hour intravenous injection.

    (A) H&E-stained image of the tumor-bearing liver tissue. The inset is the zoomed-in area of interest showing the normal tissue and tumor foci. (B and C) Corresponding LDI MSI images of DOX/PEG-MoS2 nanosheets at (B) m/z = 193.8 and (C) m/z = 321.0 in tumor-bearing liver tissue. Insets show the detailed distribution information in normal tissue and tumor foci corresponding to the zoomed-in area. (D) Merged LDI MSI images of m/z = 193.8 and m/z = 321.0 in liver tumor-bearing liver tissues. (E) Average ion intensity of DOX/PEG-MoS2 at m/z = 193.8 in normal tissue and tumor foci in (B). (F) Average drug/carrier ratio in normal tissue and tumor foci, which were obtained by calculating the average ion intensity ratio (Im/z 321.0/Im/z 193.8) in 10 randomly selected regions of normal liver tissue and tumor foci (50 pixels each), respectively. ***P < 0.01. The statistical results shown in this figure were obtained from the mice that we showed in this figure, but we have done three different mice in each group, and they all showed similar results.

  • Fig. 5 Quantification of MoS2 nanosheets in organs.

    (A) Calibration curve plotted average ion intensities of m/z = 193.8 against concentrations of MoS2 nanosheets in spleen homogenate. (B) Quantification results of bare MoS2 nanosheets in different organs varied with different time courses. (C) Comparative quantification of Mo element in different organs by LDI MS and ICP MS. The control group showed the content of Mo element in normal Kunming mice (three normal mice were tested) detected by ICP MS. (D) Quantification of MoS2 nanosheets in the lung, spleen, and liver and 4T1 tumor of 4T1 tumor model mice bearing 24-hour intravenous injection of DOX/PEG-MoS2.

Supplementary Materials

  • Supplementary material for this article is available at http://advances.sciencemag.org/cgi/content/full/4/10/eaat9039/DC1

    Supplementary Materials and Methods

    Fig. S1. Characterization of MoS2 nanosheets.

    Fig. S2. Identification of DOX fingerprint mass peak.

    Fig. S3. Average ion intensity ratios of the DOX/PEG-MoS2 with different loading ratios.

    Fig. S4. Representative LDI MS spectra in mice tissues.

    Fig. S5. LDI MSI images of tissues in normal mice.

    Fig. S6. LDI MSI images of tissues injected with bare and LA-PEG–modified MoS2 nanosheets (PEG-MoS2) in normal mice.

    Fig. S7. Suborgan distribution of MoS2 nanosheets in normal mouse spleen.

    Fig. S8. H&E-stained images of tissues from the tumor model mice.

    Fig. S9. LDI MSI images of tissues in subcutaneous implanted tumor models.

    Fig. S10. Distribution of bare MoS2 nanosheets in the liver of orthotopic H22 tumor model mice after 48-hour intravenous injection.

    Fig. S11. LDI MSI images of MoS2 nanosheets and their payload DOX in tissues of normal mice.

    Fig. S12. Representative LDI mass spectra of DOX/PEG-MoS2–injected mouse tissue slices.

    Fig. S13. Drug release from DOX/PEG-MoS2 nanosheets at different pH values as a function of time.

    Fig. S14. LDI MSI images of CNTs (carbon nanotubes) and their payload DOX in tissues.

    Fig. S15. LDI MSI images of black phosphorus nanosheets and their payload DOX in tissues.

    Fig. S16. LDI MSI images of gold nanoparticles and their payload DOX in tissues.

    Fig. S17. Standard calibration curves for bare MoS2 nanosheets in tissues.

    References (3540)

  • Supplementary Materials

    This PDF file includes:

    • Supplementary Materials and Methods
    • Fig. S1. Characterization of MoS2 nanosheets.
    • Fig. S2. Identification of DOX fingerprint mass peak.
    • Fig. S3. Average ion intensity ratios of the DOX/PEG-MoS2 with different loading ratios.
    • Fig. S4. Representative LDI MS spectra in mice tissues.
    • Fig. S5. LDI MSI images of tissues in normal mice.
    • Fig. S6. LDI MSI images of tissues injected with bare and LA-PEG–modified MoS2 nanosheets (PEG-MoS2) in normal mice.
    • Fig. S7. Suborgan distribution of MoS2 nanosheets in normal mouse spleen.
    • Fig. S8. H&E-stained images of tissues from the tumor model mice.
    • Fig. S9. LDI MSI images of tissues in subcutaneous implanted tumor models.
    • Fig. S10. Distribution of bare MoS2 nanosheets in the liver of orthotopic H22 tumor model mice after 48-hour intravenous injection.
    • Fig. S11. LDI MSI images of MoS2 nanosheets and their payload DOX in tissues of normal mice.
    • Fig. S12. Representative LDI mass spectra of DOX/PEG-MoS2–injected mouse tissue slices.
    • Fig. S13. Drug release from DOX/PEG-MoS2 nanosheets at different pH values as a function of time.
    • Fig. S14. LDI MSI images of CNTs (carbon nanotubes) and their payload DOX in tissues.
    • Fig. S15. LDI MSI images of black phosphorus nanosheets and their payload DOX in tissues.
    • Fig. S16. LDI MSI images of gold nanoparticles and their payload DOX in tissues.
    • Fig. S17. Standard calibration curves for bare MoS2 nanosheets in tissues.
    • References (3540)

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