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Nanoparticle-mediated drug delivery to tumor vasculature suppresses metastasis.


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.

SUBMITTER: Murphy EA 

PROVIDER: S-EPMC2453735 | biostudies-literature | 2008 Jul

REPOSITORIES: biostudies-literature

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Nanoparticle-mediated drug delivery to tumor vasculature suppresses metastasis.

Murphy Eric A EA   Majeti Bharat K BK   Barnes Leo A LA   Makale Milan M   Weis Sara M SM   Lutu-Fuga Kimberly K   Wrasidlo Wolfgang W   Cheresh David A DA  

Proceedings of the National Academy of Sciences of the United States of America 20080707 27


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 pancreat  ...[more]

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