Context: Glioblastoma multiforme (GBM) is the most common malignant brain tumor originating in the central nervous system. Efficient delivery of therapeutic molecules to the cells and tissues is a difficult challenge. Objective: Arginine-glycine-aspartic acid peptide (RGD)-modified nanostructured lipid carriers (NLCs) were used for the delivery of temozolomide (TMZ) into the GBM to provide a new paradigm in gliomatosis cerebri treatment. Methods:RGD-conjugated polyethylene glycol-b-distearoylphosphatidylethanolamine (PEG-DSPE) was synthesized. RGD containing, TMZ-loaded NLCs (RGD-TMZ/NLCs) were prepared. Their particle size, zeta potential, drug encapsulation efficiency (EE) and drug release behavior were evaluated. In vitro cytotoxicity study of TMZ/NLCs was tested in U87 malignant glioma cells (U87MG cells). In vivo antitumor efficacy of the carriers was evaluated on mice bearing GBM model. Results: The U87MG cells were successfully inhibited by RGD-TMZ/NLCs in vitro. RGD-TMZ/NLCs also displayed the highest antitumor efficacy in vivo than all the other formulations used for comparison. Conclusion: RGD-TMZ/NLCs were efficient in selective delivery of TMZ into U87MG cells, and inhibition efficacy is high. These RGD-modified vectors could be a superior drug delivery nanosystem to achieve therapeutic efficacy, and this research could be a new promising strategy for treatment in malignant gliomatosis cerebri.