Journal
SCIENCE
Volume 296, Issue 5577, Pages 2404-2407Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1070200
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Funding
- NCI NIH HHS [T32 CA09696, CA50286] Funding Source: Medline
- NCRR NIH HHS [P41 RR09784] Funding Source: Medline
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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 alphavbeta3-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(mu)-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 sustained regression of established primary and metastatic tumors.
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