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Proc Natl Acad Sci U S A. 2008 Jul 8;105(27):9343-8. doi: 10.1073/pnas.0803728105. Epub 2008 Jul 7.

Nanoparticle-mediated drug delivery to tumor vasculature suppresses metastasis.

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1
Department of Pathology, Moores Cancer Center, University of California at San Diego, 3855 Health Sciences Drive, La Jolla, CA 92093, USA.

Abstract

Integrin alphanubeta3 is found on a subset of tumor blood vessels where it is associated with angiogenesis and malignant tumor growth. We designed an alphanubeta3-targeted nanoparticle (NP) encapsulating the cytotoxic drug doxorubicin (Dox) for targeted drug delivery to the alphanubeta3-expressing tumor vasculature. We observed real-time targeting of this NP to tumor vessels and noted selective apoptosis in regions of the alphanubeta3-expressing tumor vasculature. In clinically relevant pancreatic and renal cell orthotopic models of spontaneous metastasis, targeted delivery of Dox produced an antimetastatic effect. In fact, alphanubeta3-mediated delivery of this drug to the tumor vasculature resulted in a 15-fold increase in antimetastatic activity without producing drug-associated weight loss as observed with systemic administration of the free drug. These findings reveal that NP-based delivery of cytotoxic drugs to the alphanubeta3-positive tumor vasculature represents an approach for treating metastatic disease.

PMID:
18607000
PMCID:
PMC2453735
DOI:
10.1073/pnas.0803728105
[Indexed for MEDLINE]
Free PMC Article
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