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Galactosylated chitosan-functionalized mesoporous silica nanoparticles for efficient colon cancer cell-targeted drug delivery

Liu, Wei, Zhu, Yongchao, Wang, Fan, Li, Xue, Liu, Xiaojing, Pang, Jingjing, Pan, Weisan·2018·Royal Society Open Science
DOI 10.1098/rsos.181027PMC PMC6304116
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Abstract

Targeted drug delivery to colon cancer cells can significantly enhance the therapeutic efficiency. Herein, we developed 5-fluorouracil (5-FU)-loaded amino-functionalized mesoporous silica nanoparticle (MSN-NH 2 )-based galactosylated chitosans (GCs), which are galactose receptor-mediated materials for colon-specific drug delivery systems. Both unmodified and functionalized nanoparticles were characterized by scanning electron microscopy, transmission electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, nitrogen sorption and dynamic light scattering. Drug loading capacity and drug release properties were determined by ultraviolet spectrophotometry. 5-FU@MSN-NH 2 /GC showed high loading capacity and possessed much higher cytotoxicity on human colon cancer cells (SW620 cells) than 5-FU@MSN-NH 2 and free 5-FU. But, MSN-NH 2 /GC did not show significant cytotoxicity. Subsequently, 5-FU@MSN-NH 2 /GC anti-cancer activity on SW620 cells in vitro was confirmed by cell apoptosis. These results are consistent with the cellular uptake test in which MSN-NH 2 /GC could specifically recognize and bind to cancer cells by the galectin-receptor recognition. But, it is found that pre-addition of galactose in the medium, leading to competitive binding to the galectin receptor of SW620 cells, resulted in a decrease in the binding of MSN-NH 2 /GC to the galectin receptor. The results demonstrated the inorganic–organic nanocomposite could be used as a promising drug delivery carrier for the targeted delivery of drug into galectin-positive colon cancer cells to improve therapeutic index while reducing side effects.

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Figure 1. TEM images of MSN (a) and MSN-NH2/GC (b).
Figure 1. TEM images of MSN (a) and MSN-NH2/GC (b).CC BY · PubMed Central
Figure 2. SEM images of MSN (a) and MSN-NH2/GC (b).
Figure 2. SEM images of MSN (a) and MSN-NH2/GC (b).CC BY · PubMed Central
Figure 3. Zeta potential measurements of MSN, MSN-NH2 and MSN-NH2/GC.
Figure 3. Zeta potential measurements of MSN, MSN-NH2 and MSN-NH2/GC.CC BY · PubMed Central
Figure 4. Low angle powder XRD of MSN, MSN-NH2 and MSN-NH2/GC.
Figure 4. Low angle powder XRD of MSN, MSN-NH2 and MSN-NH2/GC.CC BY · PubMed Central
Figure 5. FTIR spectra of MSN (a), MSN-NH2 (b), GC (c) and MSN-NH2/GC (d).
Figure 5. FTIR spectra of MSN (a), MSN-NH2 (b), GC (c) and MSN-NH2/GC (d).CC BY · PubMed Central
Figure 6. (a) Nitrogen adsorption and desorption isotherms for unmodified MSN (a), MSN-NH2 (b) and MSN-NH2/GC (c). The adsorption branch is black and the desorption branch is red. (b) The BJH pore size distributions of MSN (a) and MSN-NH2 (b).
Figure 6. (a) Nitrogen adsorption and desorption isotherms for unmodified MSN (a), MSN-NH2 (b) and MSN-NH2/GC (c). The adsorption branch is black and the desorption branch is red. (b) The BJH pore size distributions of MSN (a) and MSN-NH2 (b).CC BY · PubMed Central
Figure 7. 5-FU release profiles from 5-FU@MSN-NH2 and 5-FU@MSN-NH2/GC in pH solutions (pH = 7.4).
Figure 7. 5-FU release profiles from 5-FU@MSN-NH2 and 5-FU@MSN-NH2/GC in pH solutions (pH = 7.4).CC BY · PubMed Central
Figure 8. The fluorescence microscopy photographs of SW620 cells internalizing the FITC (a), FITC@MSN-NH2 (b), FITC@MSN-NH2/GC (c), FITC@MSN-NH2/GC+galactose (d).
Figure 8. The fluorescence microscopy photographs of SW620 cells internalizing the FITC (a), FITC@MSN-NH2 (b), FITC@MSN-NH2/GC (c), FITC@MSN-NH2/GC+galactose (d).CC BY · PubMed Central
Figure 9. The fluorescence intensity of the samples in SW620 cells (a). The uptake rates of the samples in SW620 cells (b).
Figure 9. The fluorescence intensity of the samples in SW620 cells (a). The uptake rates of the samples in SW620 cells (b).CC BY · PubMed Central
Figure 10. Cell viability assay of GC, MSN-NH2 and MSN-NH2/GC on SW620 cells at different concentrations (a). Cell inhibition rate of free 5-FU, 5-FU@MSN-NH2 and 5-FU@MSN-NH2/GC on SW620 cells at different concentrations (b).
Figure 10. Cell viability assay of GC, MSN-NH2 and MSN-NH2/GC on SW620 cells at different concentrations (a). Cell inhibition rate of free 5-FU, 5-FU@MSN-NH2 and 5-FU@MSN-NH2/GC on SW620 cells at different concentrations (b).CC BY · PubMed Central
Figure 11. Flow cytometry measurement of SW620 cells apoptosis treated with 5-FU, 5-FU@MSN-NH2 and 5-FU@MSN-NH2/GC.
Figure 11. Flow cytometry measurement of SW620 cells apoptosis treated with 5-FU, 5-FU@MSN-NH2 and 5-FU@MSN-NH2/GC.CC BY · PubMed Central
Figure 12. Mitochondrial membrane potential measurements of blank (a) free 5-FU, (b) 5-FU@MSN-NH2, (c) 5-FU@MSN-NH2/GC (d) on SW620 cells.
Figure 12. Mitochondrial membrane potential measurements of blank (a) free 5-FU, (b) 5-FU@MSN-NH2, (c) 5-FU@MSN-NH2/GC (d) on SW620 cells.CC BY · PubMed Central

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Metadata

Authors
Liu, W., Zhu, Y., Wang, F., Li, X., Liu, X., Pang, J., & Pan, W.
Affiliations
  • Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, People's Republic of China
  • Department of Pharmaceutics, School of Pharmacy, Zhengzhou University, 100 Science Avenue, Zhengzhou 450001, People's Republic of China
ORCID
Venue
Royal Society Open Science
Publisher
The Royal Society
Published
2018-12
Volume
5
Issue
12
Pages
181027
ISSN
2054-5703
DOI
10.1098/rsos.181027
PMC
PMC6304116
Cited by
59
References
0
Language
en
Licence
royalsociety.org/journals/ethics-policies/data-sharing-mining/ (tdm)
Funders
  • Zhengzhou University
  • National Natural Science Foundation of China (81473163)
  • Shenyang Pharmaceutical University

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