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Archive > Volume 30 Issue 12 > 2023,30(12):1043-1050. DOI:10.3872/j.issn.1007-385X.2023.12.002 Prev Next
Basic Research
The target killing effect of cRGD-modified Zinc-doped dendritic mesoporous silicon carrier delivering disulfiram against colorectal cancer CT26 cells
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Abstract:
Objective: To construct a cyclic arginine-glycine-aspartate (cRGD)-modified, Zn2+-doped and disulfiram-loaded dendritic mesoporous silicon nanoparticles and to preliminarily investigate its targeting and killing effects against colorectal cancer CT26 cells.Methods: Firstly, Zn2+ was anchored in the skeleton of dendritic mesoporous silicon nanoparticles by hydrothermal synthesis method,then disulfiram was loaded into the pores, and the targeting ligand cRGD was coupled to the surface of the nanoparticles to obtain functional nanoparticles DSF@Zn-DMSN-cRGD. After that, transmission electron microscopy (TEM) was used to detect the surface morphology of DSF@Zn-DMSN-cRGD, and energy spectrum scanning was further used to obtain element mapping images to verify element distribution. Laser particle size analyzer was used to detect the changes of particle size and zeta potential, and infrared spectrometer was used to detect the major chemical bonds on the surface. The morphology of carrier Zn-DMSN after being co-cultured in simulated body fluid solution (pH6.5 and pH7.4) was observed by transmission electron microscopy. Cell uptake assay was used to detect the ability of cRGD-modified Zn-DMSN to target CT26 cells. CCK-8 assay, Calcein-AM/PI staining and flow cytometry were used to detected the killing ability of DSF@Zn-DMSN-cRGD against CT26 cells and its influence on the apoptosis of CT26 cells.Results: The TEM image displayed that the surface of DSF@Zn-DMSN-cRGD was a multi-aperture structure. Element mapping images showed Zn and DSF were successfully loaded on the surface of nanoparticles. The results of infrared spectroscopy showed that cRGD was successfully coupled on the surface of DSF@Zn-DMSN. The particle size slightly increased after coupling cRGD, while the zeta potential obviously increased (P<0.000 1). The images of TEM showed that Zn-DMSN disintegrated faster in pH6.5 solution than in pH7.4 solution. The results of cell uptake experiments showed that the efficiency of CT26 cells uptaking cRGD-modified Zn-DMSN was enhanced prominently (P<0.05). After DSF@Zn-DMSN-cRGD treatment, the results of CCK-8 assay, Calcein-AM/PI staining,and flow cytometry showed that DSF@Zn-DMSN-cRGD could efficiently kill CT26 cells (all P<0.000 1) and induce apoptosis (all P<0.000 1); there was no significant damage to normal colon epithelial cells. Conclusion: DSF@Zn-DMSN-cRGD has been successfully synthesized, and its core skeleton of carrier Zn-DMSN respondes well to pH degradation. In vitro, DSF@Zn-DMSN-cRGD shows substantial targeted toxicity against colorectal cancer cell line CT26, among them, cRGD promotes the targeted endocytosis of nanoparticles by CT26 cells.
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