Proceedings of the National Academy of Sciences · 2008 · 455 citations · 26 references
PharmacyCancer BiologyOncologyDrug DeliveryNanoparticle Drug DeliveryTargeted Drug DeliveryCancer NanomedicineNanocarriers For TherapeuticsNanomedicineNanoparticle Delivery SystemsNanoparticle DesignNanoparticle FormulationsCancer NanotherapyNanoparticle DeliveryNanoparticle Drug Delivery SystemsNanoparticle Drug TargetingTargeted Nanoparticle DesignTumor Vasculature TargetingTumor-targeted Drug DeliveryVascular Targeting
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.
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Drug Delivery Systems: Entering the Mainstream
Theresa M. Allen, Pieter R. Cullis · Science · 2004 · 4.5K citations
Integrins αvβ3 and αvβ5 promote adenovirus internalization but not virus attachment
Thomas J. Wickham, Patricia Mathias, David A. Cheresh et al. · Cell · 1993 · 2.2K citations