The Preliminary Study For Targeted Therapy Of Glioma Based On MSCs As A Drug Vehicle

It was reported that mesenchymal stem cells (MSCs) could migrate ability towards solid tumor. In this study, we investigated the possibility of MSCs as a drug carrier in tumor targeting treatment by using an affinitive peptide (P1) of MSCs linked to MMPs substrate peptide (P2) and drugs.After four rounds of panning MSCs by using a Ph.D.-C7C? phage display peptide library, a high affinity peptide of MSCs was obtained. For observation we synthesize the FITC and Biotin marked-peptide (FITC-CSTNPKVLC, Bio-CSTNPKVLC) . Green fluorescence was observed on the surface of MSCs by using fluorescent microscope, when the FITC-Peptide (FITC-P1) was incubated with MSCs. The fluorescence intensity of MSC-FITC-P1 was 29.7 times higher than that of controls, and about 99.8% of MSCs was conjuncted with FITC-P1. On the results of ELISA, the value of Bio-Pl bound to MSCs was 4.05 times higher than that of blank, which confirmed the favorable affinity of Bio-Pl towards MSCs. In order to investigate the affinity and stability of Bio-Pl towards MSCs in vivo, MSCs-Bio-P1 was implanted into the periphery of tumor tissue below the skin of nude mouse. After 4 days of implantation, the slice of tumor tissue was analyzed by immunochemistry analysis. The positive staining was mainly shown in the cell membrane of MSCs.We established the glioma animal model, and the expression and enzymatic activity of matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9) in 9L glioma cells and glioma tissue were analyzed by RT-PCR, immunohistochemistry and SDS-PAGE zymography and in situ zymography. The results showed that the amount of MMP-2 and MMP-9 were positively correlated with the growth of gliomas.We designed and synthesized the FITC-P1-P2 conjugates for tumor-targeted delivery of drugs via the mediation of MMP-2 and MMP-9, both being widely known as...