Self-Illuminating 64Cu-Doped CdSe/ZnS Nanocrystals for in Vivo Tumor Imaging

Construction of self-illuminating semiconducting nanocrystals, also called quantum dots (QDs), has attracted much attention recently due to their potential as highly sensitive optical probes for biological imaging applications. Here we prepared a self-illuminating QD system by doping positron-emitting radionuclide 64Cu into CdSe/ZnS core/shell QDs via a cation-exchange reaction. The 64Cu-doped CdSe/ZnS QDs exhibit efficient Cerenkov resonance energy transfer (CRET). The signal of 64Cu can accurately reflect the biodistribution of the QDs during circulation with no dissociation of 64Cu from the nanoparticles. We also explored this system for in vivo tumor imaging. This nanoprobe showed high tumor-targeting ability in a U87MG glioblastoma xenograft model (12.7% ID/g at 17 h time point) and feasibility for in vivo luminescence imaging of tumor in the absence of excitation light. The availability of these self-illuminating integrated QDs provides an accurate and convenient tool for in vivo tumor imaging and detection.

[1]  Samuel Achilefu,et al.  Activatable probes based on distance-dependent luminescence associated with Cerenkov radiation. , 2013, Angewandte Chemie.

[2]  Zhen Cheng,et al.  Harnessing the Power of Radionuclides for Optical Imaging: Cerenkov Luminescence Imaging , 2011, The Journal of Nuclear Medicine.

[3]  Sanjiv S. Gambhir,et al.  Molecular Optical Imaging with Radioactive Probes , 2010, PloS one.

[4]  J Nucl Med , 2010 .

[5]  Yadong Yin,et al.  Cation Exchange Reactions in Ionic Nanocrystals , 2004, Science.

[6]  Vasilis Ntziachristos,et al.  Looking and listening to light: the evolution of whole-body photonic imaging , 2005, Nature Biotechnology.

[7]  Prashant K. Jain,et al.  Nanoheterostructure cation exchange: anionic framework conservation. , 2010, Journal of the American Chemical Society.

[8]  Ken-Tye Yong,et al.  Quantum Dots for Biophotonics , 2012, Theranostics.

[9]  Ya‐Ping Sun,et al.  Quantum-sized carbon dots for bright and colorful photoluminescence. , 2006, Journal of the American Chemical Society.

[10]  S. Nie,et al.  In vivo cancer targeting and imaging with semiconductor quantum dots , 2004, Nature Biotechnology.

[11]  Xiaohu Gao,et al.  Designing multifunctional quantum dots for bioimaging, detection, and drug delivery. , 2010, Chemical Society reviews.

[12]  Sanjiv S Gambhir,et al.  Self-illuminating quantum dot conjugates for in vivo imaging , 2006, Nature Biotechnology.

[13]  Zhen Cheng,et al.  In vitro and in vivo uncaging and bioluminescence imaging by using photocaged upconversion nanoparticles. , 2012, Angewandte Chemie.

[14]  Sanjiv S. Gambhir,et al.  Dual-Function Probe for PET and Near-Infrared Fluorescence Imaging of Tumor Vasculature , 2007, Journal of Nuclear Medicine.

[15]  M. Welch,et al.  In vivo transchelation of copper-64 from TETA-octreotide to superoxide dismutase in rat liver. , 2000, Bioconjugate chemistry.

[16]  H. Maeda,et al.  Exploiting the enhanced permeability and retention effect for tumor targeting. , 2006, Drug discovery today.

[17]  Kathryn E. Luker,et al.  Optical Imaging: Current Applications and Future Directions , 2007, Journal of Nuclear Medicine.

[18]  S R Cherry,et al.  Optical imaging of Cerenkov light generation from positron-emitting radiotracers , 2009, Physics in medicine and biology.

[19]  Spencer L Shorte,et al.  In vivo excitation of nanoparticles using luminescent bacteria , 2012, Proceedings of the National Academy of Sciences.

[20]  A. Alivisatos,et al.  Synthesis of PbS nanorods and other ionic nanocrystals of complex morphology by sequential cation exchange reactions. , 2009, Journal of the American Chemical Society.

[21]  J. Richard,et al.  Proton transfer at carbon. , 2001, Current opinion in chemical biology.

[22]  Robert Sinclair,et al.  Particle size, surface coating, and PEGylation influence the biodistribution of quantum dots in living mice. , 2008, Small.

[23]  Zhen Cheng,et al.  Radiation-luminescence-excited quantum dots for in vivo multiplexed optical imaging. , 2010, Small.

[24]  S. Gambhir,et al.  Quantum Dots for Live Cells, in Vivo Imaging, and Diagnostics , 2005, Science.

[25]  宁北芳,et al.  疟原虫var基因转换速率变化导致抗原变异[英]/Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A , 2005 .

[26]  Jan Grimm,et al.  Quantitative imaging of disease signatures through radioactive decay signal conversion , 2013, Nature Medicine.

[27]  Sheila N. Baker,et al.  Luminescent carbon nanodots: emergent nanolights. , 2010, Angewandte Chemie.

[28]  J. Frangioni In vivo near-infrared fluorescence imaging. , 2003, Current opinion in chemical biology.

[29]  K. Francis,et al.  Enhanced detection of myeloperoxidase activity in deep tissues through luminescent excitation of near-infrared nanoparticles , 2013, Nature Medicine.

[30]  Xiaogang Liu,et al.  Recent advances in the chemistry of lanthanide-doped upconversion nanocrystals. , 2009, Chemical Society reviews.

[31]  B. Wilson,et al.  In Vivo Fluorescence Spectroscopy and Imaging for Oncological Applications , 1998, Photochemistry and photobiology.