Studies On The Anti-glioblastoma Efficacy And Molecular Mechanism Of Resveratrol And Its Targeting Nanoparticles

Glioblastoma is the most common primary brain tumor with the highest malignant degree,which has extremely poor prognosis due to the difficulty to remove all of the tumor and the lack of reliable therapeutic drugs.Resveratrol is a kind of natural polyphenols,which has been proved that resveratrol effectively inhibits the in vitro growth of various tumor cells.More importantly,the conventional anti-tumor doses have little side effects on normal tissues and cells,which suggests that resveratrol would be an alternative ideal anti-cancer drug for temozolomide.However,the short half-life and low bioavailability in the organs after systematic administration greatly limit the application of resveratrol.The purposes of this study are 1)Combined with the specificity receptors on glioblastoma,we adopted a peptide,Pep-1,synthesized Pep-1 modified nanoparticles loaded with resveratrol(Pep-PP@Res),by evaluating its physical and chemical properties,efficacy in vivo and in vitro,hoping to effectively solve the application of resveratrol in vivo defects,improve the treatment of glioblastoma;2)To explore the therapeutic effect of resveratrol on glioblastoma and to identify its potential anti-tumor mechanism.In chapter one,the diagnosis and treatment of glioblastoma,the research status of resveratrol in anti-tumor therapy,and the progress of nanoparticle loaded resveratrol in recent years were systematically summarized and discussed.In chapter two,by using the emulsion diffusion method,blank nanoparticles(PP,Pep-PP)and Res formulations(PP@Res and Pep-PP@Res)were prepared and characterized.TEM and DLS demonstrated that the sizes of PP,Pep-PP,PP@Res,Pep-PP@Res were less than 50 nm with unimodal distribution.In vitro drug release analyses performed on Pep-PP@Res showed a p H-sensitive and time-dependent behavior.In chapter three,we conformed the target effect of Pep-1 through Fluorescence microscopy and flow cytometry.MTT study and Ed U stain and in vivo treatment of glioblastoma model proved that loading resveratrol into nanoparticles can significantly improve the inhibition of Res on glioblastoma.Meanwhile,we revealed that resveratrol may induce ROS accumulation and lead to apoptosis via activating the JNK signaling pathway in C6 cells through Annexin V/PI double dye,specific fluorescent dye,Western blot and RT-PCR.