| Objective To observe the feasibility and efficiency of MSN-PEG-IP sustained DOX in glioma targeted therapy,which was constructed by Mesoporous silica nanoparticles(MSN)via polyethylene glycol(PEG)conjugated with interleukin-13(IP).Method Immunohistochemistry and Western Blot were used to detect the expression of IL-13R?2 in gliomas and normal brain tissues,and analyze the feasibility of IL-13R?2 as a specific targeted ligand.The ability of MPI as a drug carrier for the glioma targeted therapy in vitro was analyzed by fluorescence microscopy.Glioma-bearing rat models were constructed,and injected by tail vein.Fluorescence microscopy and fluorescence spectrophotometer were used to detect the distribution of DOX in rats,to evaluate the feasibility of MSN-PEG-IP / DOX(MPI / D)for glioma targeted therapy in vivo.The changes of tumor size in tumor-bearing rats were detected by MRI,the proliferation and apoptosis of glioma were observed by immunofluorescence.Then the effect of MPI/D for glioma targeted therapy was evaluated.The MPI/D distribution of of major organs in rats was observed by transmission electron microscopy(TEM)Glioma-bearing mice were constructed and injected by tail vein,verified the targeted ability of MPI/D by in vivo fluorescence imaging;MSN/DOX(M/D)and MSN-PEG/DOX(MP/D)were used as the controls in this study.Result The results of immunohistochemistry and Western Blot showed that the expression of IL-13R?2 in gliomas was significantly higher than that in normal brain tissues,and increased with the malignant degree.The survival curves showed glioma patients with higher IL13R?2 expression were associated with a shorter survival time than patients with lower IL13R?2 expression.Which indicated IL13R?2 was suitable as a specific targeted ligand.Compared with M/D and MP/D,fluorescence microscopy and fluorescence spectrophotometer showed that DOX of each group was mainly distributed in the nucleus,the intensity of MPI/D in glioma cells and tumor area were higher than others,but there is no significant difference in the normal brain tissue and astrocytes.The results of in vivo fluorescence imaging also showed the intensity of MPI/D in the tumor area of glioma-bearing mice was the highest.TEM confirmed the content of MP/D in glioma tissue was significantly higher than normal brain tissue.MRI and immunofluorescence showed MPI/D can promote glioma cells apoptosis and inhibit proliferation in vivo,the therapeutic effect of MPI/D was the best among the three targeted drug delivery systems.Conclusion The results of this study demonstrate IL-13R?2 is a suitable specific targeted ligand.MPI as a targeted drug delivery system showed the ability to target glioma in vitro and in vivo after sustained DOX,and has definite therapeutic effect in glioma-bearing rat model,provide a new option for clinical targeted therapy of glioma. |
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