Tumor Regression by Targeted Gene Delivery to the

Efforts to influence the biology of blood vessels by gene delivery have been hampered by a lack of targeting vectors specific for endothelial cells in diseased tissues. Here we show that a cationic nanoparticle (NP) coupled to an integrin v3–targeting ligand can deliver genes selectively to angiogenic blood vessels in tumor-bearing mice. The therapeutic efficacy of this approach was tested by generating NPs conjugated to a mutant Raf gene, ATP-Raf, which blocks endothelial signaling and angiogenesis in response to multiple growth factors. Systemic injection of the NP into mice resulted in apoptosis of the tumor-associated endothelium, ultimately leading to tumor cell apoptosis and sus-tained regression of established primary and metastatic tumors. Vascular targeting offers therapeutic promise for the delivery of drugs (1) and radionuclides (2). Moreover, targeting of genes to specific blood vessels may provide complementary ap-proaches to disrupt or induce the growth of ne