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. 2021 Jan 29;11(2):343.
doi: 10.3390/nano11020343.

Real-Time Tracking of Highly Luminescent Mesoporous Silica Particles Modified with Europium β-Diketone Chelates in Living Cells

Jong-Seok Kim  1 , Sung Ki Lee  2 , Hansol Doh  3 , Myeong Yun Kim  4 , Do Kyung Kim  4
Affiliations

Real-Time Tracking of Highly Luminescent Mesoporous Silica Particles Modified with Europium β-Diketone Chelates in Living Cells

Jong-Seok Kim et al. Nanomaterials (Basel). .

Abstract

Highly luminescent europium complexes modified mesoporous silica particles (MSP) were synthesized as an imaging probes for both in-vitro diagnostic and in-vivo cellular tracking agents. Europium β-diketone chelates (4,4,4-trifluoro-l-(2-thienyl)-l,3-butanedione) trioctylphosphine europium (III) (Eu(TTA)3(P(Oct)3)3) were incorporated inside the nanocavities that existed in hierarchical MSP (Eu@MSP). The MSP and Eu@MSP on mouse bone marrow-derived macrophages (BMDMs) did not show any toxic effect. The MSP and Eu@MSP in the BMDMs were found at cytoplasm without any degradation and immunogenicity. However, both pro- and anti-inflammatory cytokines of macrophages were significantly increased when lipopolysaccharide and a high concentration (100 μg/mL) of MSP and Eu@MSP were treated simultaneously.

Keywords: beta-diketone; europium complex; inflammation; live cell image; mesoporous silica.

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Conflict of interest statement

The authors declare that they have no known conflict of interest associated with this publication and there has been no competing financial interest for this work that could have influenced its outcome.

Figures

Figure 1
Figure 1
Schematic flow diagram of the synthesis route for Eu(TTA)3(P(Oct)3)3 modified MSP by multi-step process. First, both surface and nanocavities of mesoporous silica particles (MSP) were modified with a silane coupling agent, i.e., 3-(trimethoxysilyl)propyl methacrylate (TMSPMA) as an intermediary to activate of acryloyl group. To activate the carboxylic acid, MMA, sodium styrene sulfonate (SSS), and potassium persulfate (PPS) as a catalysis are added and temperature was increased to 70 °C. β-diketone europium complex, Eu(TTA)3(P(Oct)3)3, was prepared by mixing the stoichiometric compositions of Eu3+, TTA and P(Oct)3 in EtOH. Eu(TTA)3(P(Oct)3)3@MSP (Eu@MSP) were synthesized by dropwise addition of Eu(TTA)3(P(Oct)3)3 carboxylic acid activated MSP.
Figure 2
Figure 2
Transmission electron micrograph (TEM) images of (a) mesoporous silica particles (mSiO2); (b) enlarged image of rectangle region in a); (c) scanning electron micrograph (SEM) image of mSiO2 particles; TEM images of (d) europium complexes, Eu(TTA)3(P(Oct)3)3, decorated mSiO2 (Eu(TTA)3(P(Oct)3)3@mSiO2); (e) enlarged image of rectangle region in d); (f) SEM image of Eu(TTA)3(P(Oct)3)3@mSiO2.
Figure 3
Figure 3
(a) Thermal gravimetric analysis (TGA) curves and (b) differential scanning calorimetry (DSC) thermograms of step-by-step modified samples for mSiO2, TMSPMA modified mSiO2 (TMSPMA@mSiO2), MMA modified mSiO2 (MMA@mSiO2) and Eu(TTA)3(P(Oct)3)3@mSiO2.
Figure 4
Figure 4
FTIR spectra of step-by-step modified samples for (a) mSiO2 calcined at 550 °C for 5 h; (b) TMSPMA modified mSiO2 (TMSPMA@mSiO2); (c) MMA modified mSiO2 (MMA@mSiO2); (d) Eu(TTA)3(P(Oct)3)3@mSiO2; and (e) Eu(TTA)3(P(Oct)3)3.
Figure 5
Figure 5
Concentration dependent (a) emission (λex = 308 nm) and (b) excitation (λem = 625 nm) spectra for the 5D0 → 7Fj (Eu3+, J = 0–4) transition of Eu(TTA)3(P(Oct)3)3@mSiO2. (c) excitation (λem = 625 nm) spectra for the 5D0 → 7Fj transition of Eu(TTA)3(P(Oct)3)3 and Eu(TTA)3(P(Oct)3)3@mSiO2. (d) emission (λex = 308 nm) spectra for the 5D0 → 7Fj (Eu3+, J = 0–4) transition of Eu(TTA)3(P(Oct)3)3 and Eu(TTA)3(P(Oct)3)3@mSiO2. Inserted images in (a) are mSiO2 (left) and Eu(TTA)3(P(Oct)3)3@mSiO2 (right) exposed under (i) room light, (ii) room + UV light and (iii) UV light.
Figure 6
Figure 6
Cytotoxicity of MSP and Eu@MSP to A549, HeLa, mouse bone marrow cells and mouse bone marrow-derived macrophage. (a) A549 (b) HeLa (c) mouse bone marrow cells and (d) BMDMs were plated in 96-well culture plates (1 × 104 cells/well). After 24 h, the cells were incubated with 1, 10, and 100 μg/mL of MSP and Eu@MSP, respectively, for 24 h. Cytotoxicity was evaluated using CCK-8 as described in the Materials and Methods section (n.s, no significant). (e) Detection of BMDMs cell death assessed by flow cytometry using FITC-Annexin V and PI double immunostaining. BMDMs were untreated, treated with MSP and Eu@MSP for 24 h.
Figure 7
Figure 7
MSP and Eu@MSP uptake by mouse bone marrow-derived macrophages (BMDMs). (a) Intracellular staining of europium red-coupled mSiO2 in BMDMs (Scale bar = 5 μm). BMDMs were incubated with 10 μg/mL of MSP and Eu@MSP for 4 h. The cortical F-actin and nucleus were stained using Rhodamine Texas Red and DAPI, respectively. (b) MSP and Eu@MSP uptake observation of BMDMs by live cell holotomography. BMDMs were incubated with 10 μg/mL of MSP and Eu@MSP for 4 h under live cell holotomography. White triangles indicate MSP particles. Red triangles indicated Eu@MSP.
Figure 8
Figure 8
Effects of MSP and Eu@MSP on the production of cytokines of bone marrow-derived macrophage with or without lipopolysaccharide stimulation. The production of TNF-α (a), IL-6 (b), and IL-10 (c) in the supernatant was measured by ELISA. BMDMs were treated with or without LPS (100 ng/mL) and MSP and Eu@MSP for 24 h at the indicated concentration. All data represented the mean ± standard deviation, n = 4 (** < 0.05 and *** < 0.001).
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References

    1. Cao Z., Li B., Sun L., Li L., Xu Z.P., Gu Z. 2D Layered Double Hydroxide Nanoparticles: Recent Progress toward Preclinical/Clinical Nanomedicine. Small Methods. 2020;4:1900343. doi: 10.1002/smtd.201900343. - DOI
    1. Chen X., Zhao X., Wang G. Review on marine carbohydrate-based gold nanoparticles represented by alginate and chitosan for biomedical application. Carbohydr. Polym. 2020;244:116311. doi: 10.1016/j.carbpol.2020.116311. - DOI - PubMed
    1. Arsalani S., Oliveira J., Guidelli E.J., Araujo J.F.D.F., Wiekhorst F., Baffa O. Synthesis of radioluminescent iron oxide nanoparticles functionalized by anthracene for biomedical applications. Coll. Surf. A Physicochem. Eng. Asp. 2020;602:125105. doi: 10.1016/j.colsurfa.2020.125105. - DOI
    1. Chen L., Xu J., Wang Y., Huang R. Ultra-small MoS2 nanodots-incorporated mesoporous silica nanospheres for pH-sensitive drug delivery and CT imaging. J. Mater. Sci. Technol. 2020 doi: 10.1016/j.jmst.2020.03.019. - DOI
    1. Wu S.-H., Mou C.-Y., Lin H.-P. Synthesis of mesoporous silica nanoparticles. Chem. Soc. Rev. 2013;42:3862–3875. doi: 10.1039/c3cs35405a. - DOI - PubMed

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