The Study Of Interfacial Property Of DNA And Its Based Nano Drug Carrier For Targeting Glioblastoma

Worldwide,the incidence of malignant brain tumor maintains at a high level and the malignant glioma is one of the most common and highest fatality rate of brain tumors.Because of the strong permeability of malignant glioma,it is difficult to cure completely.Patients usually appear poor prognosis,and the median survival period is less than 16 months on average.Obviously,it is an urgent need to create an effective drug delivery system for targeting malignant glioma.DNA is a part of human beings,so that it is biocompatible and non-cytotoxicity,and it is easy to modify with functional molecules.Tumor penetrating peptide used in our study is a linear peptide chosen by the phage display technology,which has been confirmed a specific ligand of NRP-1(a kind of transmembrane glycoprotein over expressed on both glioma cells and tumor vascular endothelial cells).So,in our study,we plan to modify tumor penetrating peptide onto DNA nanostructures to create a targeting nano drug delivery system.Via loading DOX in this nano drug carrier,we can achieve the goal of inhibiting the tumor growth.1)In this study,we synthesized double-strand DNA and tetrahedron DNA via self-assembly and did some further modification on tetrahedron DNA.Then we carried out some property studies on these DNA nanostructures.It showed that DNA nanostructures had reversible structural changes when the p H changed and it could be utilized for controlling release in tumor tissue.2)We studied the targeting ability of these three kinds of DNA nanostructures in the second part,and U87 MG cells and HEK293 cells were utilized.The results indicated that both tumor cells and normal cells had excellent uptake of TDN,and the process of endocytosis reached a balance at 6h.Tumor penetrating peptide enhanced the targeting ability of TDN,and the fluorescent intensity of p-TDN was almost 3.5 times compared with TDN in vivo study.3)In the third part,we studied the pharmacodynamics of these three kinds of DNA nanostructure.The IC50 of DOX@Ds,DOX@TDN,DOX@p-TDN and DOX were 13.312?M,4.785?M,2.478?M and 1.224?M in U87 MG cells after 48 h.With the help of tumor penetrating peptide,p-TDN showed stronger cytotoxicity,while it didn't have any influence in the control group of normal cells.In our study,we brought DNA and tumor penetrating peptide together in the study of nano drug delivery system targeting brain tumor,and got outstanding achievements.It would provide a new approach in the study of glioblastoma.