期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 105, 期 27, 页码 9343-9348出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0803728105
关键词
antiangiogenic; intravital microscopy; pancreatic cancer; renal cell carcinoma; liposome
资金
- NCI NIH HHS [P01 CA078045, P01-CA104898, U54 CA119335, P01 CA104898, P01-CA078045, U54-CA119335] Funding Source: Medline
Integrin alpha nu beta 3 is found on a subset of tumor blood vessels where it is associated with angiogenesis and malignant tumor growth. We designed an alpha nu beta 3-targeted nanoparticle (NP) encapsulating the cytotoxic drug doxorubicin (Dox) for targeted drug delivery to the alpha nu beta 3-expressing tumor vasculature. We observed real-time targeting of this NP to tumor vessels and noted selective apoptosis in regions of the alpha nu beta 3-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, alpha nu beta 3-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 alpha nu beta 3-positive tumor vasculature represents an approach for treating metastatic disease.
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