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Effects of gestational age and surface modification on materno-fetal transfer of nanoparticles in murine pregnancy

Yang, Hui, Sun, Cuiji, Fan, Zhenlin, Tian, Xin, Yan, Liang, Du, Libo, Liu, Yang, Chen, Chunying, Liang, Xing-jie, Anderson, Gregory J., Keelan, Jeffrey A., Zhao, Yuliang, Nie, Guangjun·2012·Scientific Reports
DOI 10.1038/srep00847PMC PMC3496197
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Figure 1 Characterization of Au-Ft, Au13-PEG and Au13-CT nanoparticles. (a) Schematic illustration of the synthesized Au-nanoparticles (Au-Ft, Au13-PEG and Au13-CT); (b) Images of suspended Au-nanoparticles in PBS; (c) Cryo-electron microscopy (Cryo-EM) image and size distribution of Au-Ft, and TEM images of Au13-PEG and Au13-CT and their corresponding size distributions; (d) Zeta potential of Au-Ft, Au13-PEG and Au13-CT in PBS; (e) Particle numbers and Au concentrations of the three nanoparticles used in these studies.
Figure 1 Characterization of Au-Ft, Au13-PEG and Au13-CT nanoparticles. (a) Schematic illustration of the synthesized Au-nanoparticles (Au-Ft, Au13-PEG and Au13-CT); (b) Images of suspended Au-nanoparticles in PBS; (c) Cryo-electron microscopy (Cryo-EM) image and size distribution of Au-Ft, and TEM images of Au13-PEG and Au13-CT and their corresponding size distributions; (d) Zeta potential of Au-Ft, Au13-PEG and Au13-CT in PBS; (e) Particle numbers and Au concentrations of the three nanoparticles used in these studies.CC BY-NC-ND · PubMed Central
Figure 2 Au accumulation in fetuses and extraembyronic tissues (EET) after a single dose of Au-nanoparticle preparation at different stages of gestation. Au-Ft (a), Au13-PEG (b) and Au13-CT (c) were administered from E5.5 to E15.5. Au content was evaluated by ICP-MS 5 h after Au administration. (d) The ratios of Au in fetus/EET after administration of different nanoparticles at different gestation stages. The dynamic changes in Au concentration in fetuses and EET are shown for (e) Au-Ft, (f) Au13-PEG, and (g) Au13-CT. (h) Total Au content in fetuses after one administration of Au-nanoparticles to pregnant mice at E8.5. The dynamic changes in Au concentrations in fetuses and EET after Au-Ft injection at E11.5 are shown in (i). Each data set represents the mean ± s.d. (n = 6).
Figure 2 Au accumulation in fetuses and extraembyronic tissues (EET) after a single dose of Au-nanoparticle preparation at different stages of gestation. Au-Ft (a), Au13-PEG (b) and Au13-CT (c) were administered from E5.5 to E15.5. Au content was evaluated by ICP-MS 5 h after Au administration. (d) The ratios of Au in fetus/EET after administration of different nanoparticles at different gestation stages. The dynamic changes in Au concentration in fetuses and EET are shown for (e) Au-Ft, (f) Au13-PEG, and (g) Au13-CT. (h) Total Au content in fetuses after one administration of Au-nanoparticles to pregnant mice at E8.5. The dynamic changes in Au concentrations in fetuses and EET after Au-Ft injection at E11.5 are shown in (i). Each data set represents the mean ± s.d. (n = 6).CC BY-NC-ND · PubMed Central
Figure 3 Au accumulation as a percentage of total recovered dose in maternal liver, extraembyronic tissues (EET) and fetuses after Au-nanoparticle preparation at E7.5 and E11.5. Au-Ft (a), Au13-PEG (b) and Au13-CT (c) were administered at E7.5 and 11.5. Au content (mean ± s.d.) was evaluated by ICP-MS 5 h after Au administration. *, P<0.5; ** P<0.001, E11.5 vs. E7.5 (ANOVA, n = 6).
Figure 3 Au accumulation as a percentage of total recovered dose in maternal liver, extraembyronic tissues (EET) and fetuses after Au-nanoparticle preparation at E7.5 and E11.5. Au-Ft (a), Au13-PEG (b) and Au13-CT (c) were administered at E7.5 and 11.5. Au content (mean ± s.d.) was evaluated by ICP-MS 5 h after Au administration. *, P<0.5; ** P<0.001, E11.5 vs. E7.5 (ANOVA, n = 6).CC BY-NC-ND · PubMed Central
Figure 4 Biodistribution of Au-nanoparticles in fetal and EET. Fetal Au accumulation was seen by X-ray microprobe synchrotron imaging near the implantation site (red arrows) and uterine wall (c), while Cu (as negative control) showed low and uniformed distribution in the entire fetus (b and d), at E8.5. Scale bar is 1 mm. Hematoxylin eosin (H&E) staining (e) of a corresponding section shows the uterine shape and orientation. CNT refers to the control group. Intrinsic Au fluorescence was observed in the fetal and placental tissue sections at E8.5 (f-k) and E11.5 (l-q). No apparent Au-Ft fluorescence was observed in the fetal tissue at E11.5. Shown are red Au-Ft fluorescence (f, i, l, o), blue Hoechst 33342 labeled nuclei (g, j, m, p), and merged images (h, k, n, q). The scale bar is 8 μm.
Figure 4 Biodistribution of Au-nanoparticles in fetal and EET. Fetal Au accumulation was seen by X-ray microprobe synchrotron imaging near the implantation site (red arrows) and uterine wall (c), while Cu (as negative control) showed low and uniformed distribution in the entire fetus (b and d), at E8.5. Scale bar is 1 mm. Hematoxylin eosin (H&E) staining (e) of a corresponding section shows the uterine shape and orientation. CNT refers to the control group. Intrinsic Au fluorescence was observed in the fetal and placental tissue sections at E8.5 (f-k) and E11.5 (l-q). No apparent Au-Ft fluorescence was observed in the fetal tissue at E11.5. Shown are red Au-Ft fluorescence (f, i, l, o), blue Hoechst 33342 labeled nuclei (g, j, m, p), and merged images (h, k, n, q). The scale bar is 8 μm.CC BY-NC-ND · PubMed Central
Figure 5 TEM images of placenta and fetal tissues after Au-nanoparticle administration. Au13-PEG or Au13-CT nanoparticles were intravenously injected into pregnant mice at E8.5 and E11.5. Au-nanoparticles were present in the fetus (a, e) and the placenta (b, f) of E8.5 mice, as well as the placenta (d, h) of E11.5 mice, but not in the fetus at E11.5 (c, g); amplified images are shown in the inserts. The scale bar is 1 μm.
Figure 5 TEM images of placenta and fetal tissues after Au-nanoparticle administration. Au13-PEG or Au13-CT nanoparticles were intravenously injected into pregnant mice at E8.5 and E11.5. Au-nanoparticles were present in the fetus (a, e) and the placenta (b, f) of E8.5 mice, as well as the placenta (d, h) of E11.5 mice, but not in the fetus at E11.5 (c, g); amplified images are shown in the inserts. The scale bar is 1 μm.CC BY-NC-ND · PubMed Central
Figure 6 In vivo fluorescence images of pregnant mice following Au-Ft administration at E8.5. Au-Ft was administered to pregnant mice at 7.2 μg/g body weight and the images show the fluorescence signal from embryonic tissue 5 h after injection. In vivo bright field (BF) and fluorescence (Fluo) images of control mouse without Au-Ft treatment (a, b); Au-Ft treated mouse (c, d). After in vivo imaging, the mice were sacrificed and the ventral skin, muscle and intestines were removed to expose the organs for in situ imaging (e–h). In situ BF and Fluo images of Au-Ft treated mouse (g, h); control mouse without Au-Ft treatment (e, f). H, heart; Lu, lung; Li, liver; S, spleen; U, uterus. The images are representative of four mice administered with Au-Ft.
Figure 6 In vivo fluorescence images of pregnant mice following Au-Ft administration at E8.5. Au-Ft was administered to pregnant mice at 7.2 μg/g body weight and the images show the fluorescence signal from embryonic tissue 5 h after injection. In vivo bright field (BF) and fluorescence (Fluo) images of control mouse without Au-Ft treatment (a, b); Au-Ft treated mouse (c, d). After in vivo imaging, the mice were sacrificed and the ventral skin, muscle and intestines were removed to expose the organs for in situ imaging (e–h). In situ BF and Fluo images of Au-Ft treated mouse (g, h); control mouse without Au-Ft treatment (e, f). H, heart; Lu, lung; Li, liver; S, spleen; U, uterus. The images are representative of four mice administered with Au-Ft.CC BY-NC-ND · PubMed Central

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Authors
Yang, H., Sun, C., Fan, Z., Tian, X., Yan, L., Du, L., Liu, Y., Chen, C., Liang, X.-J., Anderson, G. J., Keelan, J. A., Zhao, Y., & Nie, G.
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2012-11-13
Volume
2
Issue
1
ISSN
2045-2322
DOI
10.1038/srep00847
PMC
PMC3496197
Cited by
124
References
3
Language
en
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