Publication Date:
2002-06-29
Description:
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, ATPmu-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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hood, John D -- Bednarski, Mark -- Frausto, Ricardo -- Guccione, Samira -- Reisfeld, Ralph A -- Xiang, Rong -- Cheresh, David A -- CA50286/CA/NCI NIH HHS/ -- P41 RR09784/RR/NCRR NIH HHS/ -- T32 CA09696/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2002 Jun 28;296(5577):2404-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12089446" target="_blank"〉PubMed〈/a〉
Keywords:
Adenosine Triphosphate/metabolism
;
Animals
;
Apoptosis
;
Cations
;
Endothelium, Vascular/cytology/metabolism/pathology
;
Gene Targeting
;
Gene Transfer Techniques
;
Genetic Therapy/*methods
;
Genetic Vectors
;
Humans
;
In Situ Nick-End Labeling
;
Ligands
;
Lipids
;
Melanoma, Experimental/blood supply/pathology/therapy
;
Mice
;
Mice, Inbred BALB C
;
Mutation
;
*Nanotechnology
;
Neoplasm Metastasis
;
Neoplasm Transplantation
;
Neoplasms, Experimental/blood supply/pathology/*therapy
;
Neovascularization, Pathologic/pathology/*therapy
;
Proto-Oncogene Proteins c-raf/*genetics/metabolism
;
Random Allocation
;
Receptors, Vitronectin/*metabolism
;
Tumor Cells, Cultured
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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