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.