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The treatment of glioma is a great challenge because of the existence of the blood-brain barrier(BBB).In order to reduce toxicity to the normal brain tissue and achieve efficient treatment,it is also important for drugs to specifically accumulate in the glioma foci and penetrate into the tumor core after entering into the brain.In this study,a specific ligand cyclic RGD peptide was conjugated to a cell penetrating peptide R8 to develop a multifunctional peptide R8-RGD.R8-RGD increased the cellular uptake of liposomes by 2-fold and nearly 30-fold compared to separate R8 and RGD respectively,and displayed effective penetration of three-dimensional glioma spheroids and BBB model in vitro.In vivo studies showed that R8-RGD-lipo could be efficiently delivered into the brain and selectively accumulated in the glioma foci after systemic administration in C6 glioma bearing mice.When paclitaxel(PTX)was loaded in liposomes,R8-RGD-lipo could induce the strongest inhibition and apoptosis against C6 cells and finally achieved the longest survival in intracranial C6 glioma bearing mice.In conclusion,all the results indicated that the tandem peptide R8-RGD was a promising ligand possessing multi functions including BBB transporting,glioma targeting and tumor penetrating.And R8-RGD-lipo was proved to be a potential anti-glioma drug delivery system.