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Proceedings Paper

Real-time visualization of RGD-quantum dot binding in tumor neovasculature using intravital microscopy in multiple living mouse models
Author(s): Bryan Ronain Smith; Zhen Cheng; Abhijit De; Ai Leen Koh; Robert Sinclair; Sanjiv Sam Gambhir
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Paper Abstract

Quantum dots (Qdots) have become ubiquitous in biomedical research due to their excellent brightness, photostability, monodispersity, and fluorescent yield. Furthermore, they have become increasingly useful as imaging agents which are valuable for answering molecular questions in living subjects. However, little is currently known about how nanoparticles such as Qdots interact at the microscale within the vasculature and tumor microenvironments in living subjects. In order to further our understanding of the dynamic processes involved in Qdot targeting in the intact tumor, we developed an in vivo binding assay to visualize and fully elucidate this approach using a variety of animal models and tumor types. We employed argine-glycine-aspartic acid (RGD) peptides to specifically target the αvβ3 integrins which are expressed on the surface of endothelial cells comprising newly formed or forming blood vessels; RGD peptides were conjugated to the Qdot surface. Exploiting intravital microscopy with subcellular-level resolution, we directly observed and recorded the binding of nanoparticle conjugates in two different murine models, using three different tumor cell lines. Using this generalizable approach, we learned that RGD-qdots unexpectedly bind to tumor blood vessels in all models tested only as aggregates rather than individually. Understanding these issues on the microscale using such techniques will provide a platform for the rational design of molecularly-targeted nanoparticles including Qdots. This is critical for nanoparticles to become a valuable research tool with the potential to become clinically valuable imaging and therapeutic agents, particularly for ensuring regulatory approval of such nanoparticles.

Paper Details

Date Published: 3 March 2009
PDF: 12 pages
Proc. SPIE 7189, Colloidal Quantum Dots for Biomedical Applications IV, 718915 (3 March 2009); doi: 10.1117/12.809578
Show Author Affiliations
Bryan Ronain Smith, Stanford Univ. School of Medicine (United States)
Zhen Cheng, Stanford Univ. School of Medicine (United States)
Abhijit De, Stanford Univ. School of Medicine (United States)
Ai Leen Koh, Stanford Univ. (United States)
Robert Sinclair, Stanford Univ. (United States)
Sanjiv Sam Gambhir, Stanford Univ. School of Medicine (United States)

Published in SPIE Proceedings Vol. 7189:
Colloidal Quantum Dots for Biomedical Applications IV
Marek Osinski; Thomas M. Jovin M.D.; Kenji Yamamoto M.D., Editor(s)

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