Real-Time Intravital Imaging of RGD−Quantum Dot Binding to Luminal Endothelium in Mouse Tumor Neovasculature Export

@article{citeulike:3383171, abstract = {Abstract: Nanoscale materials have increasingly become subject to intense investigation for use in cancer diagnosis and therapy. However, there is a fundamental dearth in cellular-level understanding of how nanoparticles interact within the tumor environment in living subjects. Adopting quantum dots (qdots) for their excellent brightness, photostability, monodispersity, and fluorescent yield, we link arginineglycineaspartic acid (RGD) peptides to target qdots specifically to newly formed/forming blood vessels expressing ±v²3 integrins. Using this model nanoparticle system, we exploit intravital microscopy with subcellular (\~{}0.5 µm) resolution to directly observe and record, for the first time, the binding of nanoparticle conjugates to tumor blood vessels in living subjects. This generalizable method enabled us to show that in this model qdots do not extravasate and, unexpectedly, that they only bind as aggregates rather than individually. This level of understanding is critical on the path toward ensuring regulatory approval of nanoparticles in humans for disease diagnostics and therapeutics. Equally vital, the work provides a platform by which to design and optimize molecularly targeted nanoparticles including quantum dots for applications in living subjects.}, address = {The Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, and Department of Materials Science and Engineering, Stanford University, Stanford, California 94305, and Department of Bioengineering, Stanford University School of Medicine, Stanford, California 94305}, author = {Smith, Bryan R. and Cheng, Zhen and De, Abhijit and Koh, Ai L. and Sinclair, Robert and Gambhir, Sanjiv S.}, citeulike-article-id = {3383171}, citeulike-linkout-0 = {http://dx.doi.org/10.1021/nl080141f}, citeulike-linkout-1 = {http://pubs.acs.org/doi/abs/10.1021/nl080141f}, doi = {10.1021/nl080141f}, journal = {Nano Lett.}, keywords = {ccne-grant, quantum-dot, rgd-peptide, stanford-ccne, tumor}, month = {September}, number = {9}, pages = {2599--2606}, posted-at = {2008-10-07 16:45:24}, priority = {2}, title = {Real-Time Intravital Imaging of RGD\&\#x2212;Quantum Dot Binding to Luminal Endothelium in Mouse Tumor Neovasculature}, url = {http://dx.doi.org/10.1021/nl080141f}, volume = {8}, year = {2008} }

TY - JOUR ID - citeulike:3383171 L3 - citeulike-article-id:3383171 N2 - Abstract: Nanoscale materials have increasingly become subject to intense investigation for use in cancer diagnosis and therapy. However, there is a fundamental dearth in cellular-level understanding of how nanoparticles interact within the tumor environment in living subjects. Adopting quantum dots (qdots) for their excellent brightness, photostability, monodispersity, and fluorescent yield, we link arginineglycineaspartic acid (RGD) peptides to target qdots specifically to newly formed/forming blood vessels expressing ±v²3 integrins. Using this model nanoparticle system, we exploit intravital microscopy with subcellular (~0.5 µm) resolution to directly observe and record, for the first time, the binding of nanoparticle conjugates to tumor blood vessels in living subjects. This generalizable method enabled us to show that in this model qdots do not extravasate and, unexpectedly, that they only bind as aggregates rather than individually. This level of understanding is critical on the path toward ensuring regulatory approval of nanoparticles in humans for disease diagnostics and therapeutics. Equally vital, the work provides a platform by which to design and optimize molecularly targeted nanoparticles including quantum dots for applications in living subjects. IS - 9 JF - Nano Lett. AD - The Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, and Department of Materials Science and Engineering, Stanford University, Stanford, California 94305, and Department of Bioengineering, Stanford University School of Medicine, Stanford, California 94305 EP - 2606 TI - Real-Time Intravital Imaging of RGD−Quantum Dot Binding to Luminal Endothelium in Mouse Tumor Neovasculature VL - 8 SP - 2599 KW - ccne-grant KW - quantum-dot KW - rgd-peptide KW - stanford-ccne KW - tumor AU - Smith, Bryan AU - Cheng, Zhen AU - De, Abhijit AU - Koh, Ai AU - Sinclair, Robert AU - Gambhir, Sanjiv PY - 2008/09/10/ UR - http://dx.doi.org/10.1021/nl080141f ER -