Important advances have been made within in past few years in the treatment of glioma, however, the longterm prognosis after resection of glioma remains unsatisfactory as a result of a high incidence of recurrence. To solve this problem, many biologic therapies have been investigated. In the present study, we report a nanoparticle with properties for dual targeting of tumor cells and the neovasculature. The nanoparticle comprises encoding vasohibin and RGD 12-mer cationic peptide RKKRRQRRRRGD (Tat49-57RGD) peptides, which a nuclear nanoparticle within an extranuclear peptide envelope. Our results demonstrate that the nanoparticle could prevent tumor angiogenesis and inhibit tumor growth via attenuating neovasculature formation and inducing tumor apoptosis. Therefore, the dual targeting strategy of tumor cells and neovasculature represents an integrative approach in glioma therapy. This can be extended to additional agents to target multiple signal pathways or distinct tumor compartments.