Near-infrared fluorescence (NIRF)-based optical imaging of human cancers has several advantages over standard imaging techniques in that it is extremely sensitive, inexpensive, and robust;involves no harmful radiation;and allows real-time visualization. The development of well-validated NIRF imaging probes may lead to this new modality becoming clinically viable for molecular imaging. Recent advances in nanotechnology are likely to substantially accelerate the discovery of new NIRF imaging agents that can not only provide increased signal intensity, but also target or """"""""report"""""""" both the presence and the biologic activity of tumor-specific biomarkers. In this application, U. T. M. D Anderson Cancer Center, a leading institution in cancer research and patient care, and Eastman Kodak Co., a world leader in the fabrication of optical dyes and nanoparticles, will team to develop novel nanoparticles for molecular optical imaging applications. Our goals are to systematically investigate the in vivo pharmacologic properties of nanoparticles derived from Kodak's platform technology, and to design and develop nanoparticles that use targeting, enzyme activation, or a combination of both features to achieve significant improvements in the sensitivity and specificity of cancer detection.
Our specific aims are 1) to synthesize and characterize polymer-shelled silica nanoparticles and cross-linked PEG nanoparticles suitable for NIRF imaging;2) to establish the effect of particle characteristics on the pharmacokinetics, biodistribution, clearance, extravasation, and intratumoral distribution of NIRF nanoparticles;3) to establish the stability and signal intensity of NIRF nanoparticles in vivo and the specificity of their retention in tumors;4) to construct NIRF nanoparticles targeted to angiogenic blood vessels and to tumor cell-associated surface receptors;and 5) to develop smart, activatable NIRF nanoparticles and to combine homing ligand and molecular beacon designs in a single nanoparticulate system. By using a combination of nuclear and optical imaging, autoradiography, and fluorescence microscopy, we expect to provide detailed insights into the pharmacologic properties of NIRF nanoparticles, with the ultimate goal of obtaining nanoparticles that are effective and practical for molecular optical imaging of human cancers.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Special Emphasis Panel (ZCA1-SRRB-C (O1))
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Grodzinski, Piotr
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University of Texas MD Anderson Cancer Center
Other Domestic Higher Education
United States
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Li, Chun (2014) A targeted approach to cancer imaging and therapy. Nat Mater 13:110-5
Zhang, Rui; Huang, Miao; Zhou, Min et al. (2013) Annexin A5-functionalized nanoparticle for multimodal imaging of cell death. Mol Imaging 12:182-90
Tian, Mei; Lu, Wei; Zhang, Rui et al. (2013) Tumor uptake of hollow gold nanospheres after intravenous and intra-arterial injection: PET/CT study in a rabbit VX2 liver cancer model. Mol Imaging Biol 15:614-24
You, Jian; Zhang, Rui; Zhang, Guodong et al. (2012) Photothermal-chemotherapy with doxorubicin-loaded hollow gold nanospheres: A platform for near-infrared light-trigged drug release. J Control Release 158:319-28
Zhang, Guodong; Zhang, Rui; Melancon, Marites P et al. (2012) The degradation and clearance of Poly(N-hydroxypropyl-L-glutamine)-DTPA-Gd as a blood pool MRI contrast agent. Biomaterials 33:5376-83
Zhao, Jun; Song, Shaoli; Zhong, Meng et al. (2012) Dual-Modal Tumor Imaging via Long-Circulating Biodegradable Core-Crosslinked Polymeric Micelles. ACS Macro Lett 1:150-153
Lu, Wei; Xiong, Chiyi; Zhang, Rui et al. (2012) Receptor-mediated transcytosis: a mechanism for active extravascular transport of nanoparticles in solid tumors. J Control Release 161:959-66
Ku, Geng; Zhou, Min; Song, Shaoli et al. (2012) Copper sulfide nanoparticles as a new class of photoacoustic contrast agent for deep tissue imaging at 1064 nm. ACS Nano 6:7489-96
Melancon, Marites P; Elliott, Andrew M; Shetty, Anil et al. (2011) Near-infrared light modulated photothermal effect increases vascular perfusion and enhances polymeric drug delivery. J Control Release 156:265-72
Tian, Mei; Wen, Xiaoxia; Jackson, Edward F et al. (2011) Pharmacokinetics and magnetic resonance imaging of biodegradable macromolecular blood-pool contrast agent PG-Gd in non-human primates: a pilot study. Contrast Media Mol Imaging 6:289-97

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