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. 2020 Jun 16:11:898.
doi: 10.3389/fphar.2020.00898. eCollection 2020.

Preparation of RGD Peptide/Folate Acid Double-Targeted Mesoporous Silica Nanoparticles and Its Application in Human Breast Cancer MCF-7 Cells

Huijie Yan  1 , Yun You  1 , Xinjian Li  1 , Lei Liu  1 , Fengqian Guo  1 , Qiongling Zhang  1 , Dewen Liu  1 , Yan Tong  1 , Shilan Ding  1 , Jinyu Wang  1
Affiliations

Preparation of RGD Peptide/Folate Acid Double-Targeted Mesoporous Silica Nanoparticles and Its Application in Human Breast Cancer MCF-7 Cells

Huijie Yan et al. Front Pharmacol. .

Abstract

Pharmacological relevance: Paclitaxel (PTX) is currently the only botanical drug that can control the growth of cancer cells. Paclitaxel is widely used in the treatment of breast cancer, ovarian cancer, uterine cancer, non-small cell lung cancer and other cancers.

Aim: Folate receptor and integrin α v β 3 are highly expressed on the surface of human breast cancer cells MCF-7. Folic acid and arginine-glycine-aspartate (Arg-Gly-Asp, RGD) tripeptide sequence have a high affinity for folate receptor and integrin α v β 3, respectively. To enhance the effect on breast cancer, we constructed the folate acid and RGD peptide dual-targeted (MSNs-NH2-FA-RGD) drug-carrier based on mesoporous silica nanoparticles.

Methods: The structure of mesoporous nanocarriers was characterized by Fourier transform infrared spectroscopy, nitrogen adsorption-desorption analysis, transmission electron microscopy, laser particle size analyzer, and thermogravimetric analysis. Paclitaxel was chosen as the model drug. The targeting-ability was verified by observing the uptake of mesoporous carriers loaded with rhodamine in MCF-7, MCF-10A, and HeLa cells using a fluorescence microscope. The cytotoxicity of the blank carrier MSNs-NH2-FA-RGD and the efficacy of the drug carrier PTX@MSNs-NH2-FA-RGD were assessed by cell experiments.

Results: The characterization showed successful construction of a dual-targeted mesoporous silica nanocarrier. Obvious differences were detected in the fluorescence intensity of the three cell lines. The results of the pharmacological tests indicated that the blank nanoparticles do not cause any apparent toxicity on these cells. The IC50 of free PTX and PTX@MSNs-NH2-FA-RGD on MCF-7 cells line treated for 48 h were 35.25±2.57 ng·ml-1 and 22.21±3.4 ng·ml-1 respectively, which indicated that the inhibitory efficacy of PTX@MSNs-NH2-FA-RGD on MCF-7 was 1.6 times than that of free PTX.

Conclusions: The dual-targeted nanocarrier MSNs-NH2-FA-RGD could target breast cancer cells, and sever as a potential candidate in future of drug development.

Keywords: MCF-7 cells; RGD peptide; active targeted; folic acid; mesoporous silica; paclitaxel.

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Figures

Figure 1
Figure 1
Schematic illustration of preparation process of MSNs-NH2-FA-RGD.
Figure 2
Figure 2
TEM images of (A) MSNs and (B) MSNs-NH2-FA-RGD. (C) Particle size distribution of MSNs and MSNs-NH2-FA-RGD in deionized water. (D) Zeta potential of MSNs, MSNs-NH2, MSNs-NH2-FA, and MSNs-NH2-FA-RGD in deionized water.
Figure 3
Figure 3
FTIR spectra (A) and thermograms (B) of MSNs (a), MSNs-NH2 (b), MSNs-NH2-FA (c), and MSNs-NH2-FA-RGD (d).
Figure 4
Figure 4
Nitrogen adsorption-desorption isotherms of MSNs, MSNs-NH2, MSNs-NH2-FA, and MSNs-NH2-FA-RGD.
Figure 5
Figure 5
Cell viability of MCF-7 cells incubation with MSNs-NH2-FA-RGD at different concentrations (µg·ml-1) after 24 h and 48 h.
Figure 6
Figure 6
Cell viability of HeLa (A), MCF-7 (B) and MCF-10A (C) cells after 24 h incubation with MSNs-NH2, MSNs-NH2-FA and MSNs- NH2-FA-RGD at 20 µg·ml-1.
Figure 7
Figure 7
Fluorescence microscopy images of MCF-10A cells incubation with RhB@MSNs-NH2, RhB@MSNs-NH2-FA, and RhB@MSNs-NH2-FA-RGD for 4 h. Blue fluorescence field: nucleus; green fluorescence field: cytoplasm; red fluorescence field: a dye used to label nanocarriers. Scale bar: 20 μm.
Figure 8
Figure 8
Fluorescence microscopy images of HeLa cells incubation with RhB@MSNs-NH2, RhB@MSNs-NH2-FA, and RhB@MSNs-NH2-FA-RGD for 4 h. Blue fluorescence field: nucleus; green fluorescence field: cytoplasm; red fluorescence field: a dye used to label nanocarriers. Scale bar: 20 μm.
Figure 9
Figure 9
Fluorescence microscopy images of MCF-7 cells incubation with RhB@MSNs-NH2, RhB@MSNs-NH2-FA, and RhB@MSNs-NH2-FA-RGD for 4 h. Blue fluorescence field: nucleus; green fluorescence field: cytoplasm; red fluorescence field: a dye used to label nanocarriers. Scale bar: 20 μm.
Figure 10
Figure 10
Cytotoxicity for free PTX and PTX@MSNs-NH2-FA-RGD at different concentrations (ng·ml-1) against MCF-7 cells evaluated at 24 h (A) and 48 h (B). (**p < 0.01, *p < 0.05 as compared with the data of control group; ##p < 0.01, #p < 0.05 when PTX group compared with PTX@MSNs-NH2-FA-RGD at the same concentration).
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