To turn miRNA into therapeutics, it is critical to deliver antagomiRs or miRNA mimics specifically into target cells. Endothelial cells in the tumor microenvironment have been actively targeted in vivo for miRNA delivery. The cyclic Arginine-Glycine-Aspartic acid (cRGD) peptide coupled nanoparticle is most widely used. The cRGD could bind to integrin αvβ3 and αvβ5, which are present on tumor ECs, as well as on certain tumor cells. Studies have reported that systemic administration of anti-miR-296, anti-miRNA-132 or miR-7 mimics using the cRGD modified nanoparticles strongly reduced angiogenesis and tumor burden in mice, offering promise for miRNA-based anti-tumor therapeutic [86, 119, 120]. In addition to cRGD modification, anti-angiogenic effect was achieved by using miRNA- incoporated nanoparticles bearing Ala-Pro-Arg-Pro-Gly (APRPG) peptide as well. APRPG has an affinity for VEGFR-1, which is overexpressed on ECs and certain cancer cells . In vivo delivery of miR-499 via APRPG-PEG-modified lipoplexes accumulated in both angiogenic vessels and cancer cells, resulting in the downregulation of miR-499 targeted proteins and inhibition of tumor growth and angiogenesis .