Emitting/Sensitizing Ions Spatially Separated Lanthanide Nanocrystals for Visualizing Tumors Simultaneously through Up- and Down-Conversion Near-Infrared II Luminescence In Vivo.

Near-infrared lights have received increasing attention regarding imaging applications owing to their large tissue penetration depth, high spatial resolution, and outstanding signal-to-noise ratio, particularly those falling in the second near-infrared window (NIR II) of biological tissues. Rare earth nanoparticles containing Er3+ ions are promising candidates to show up-conversion luminescence in the first near-infrared window (NIR I) and down-conversion luminescence in NIR II as well. However, synthesizing particles with small size and high NIR II luminescence quantum yield (QY) remains challenging. Er3+ ions are herein innovatively combined with Yb3+ ions in a NaErF4 @NaYbF4 core/shell manner instead of being codoped into NaLnF4 matrices, to maximize the concentration of Er3+ in the emitting core. After further surface coating, NaErF4 @NaYbF4 @NaYF4 core/shell/shell particles are obtained. Spectroscopy studies are carried out to show the synergistic impacts of the intermediate NaYbF4 layer and the outer NaYF4 shell. Finally, NaErF4 @NaYbF4 @NaYF4 nanoparticles of 30 nm with NIR II luminescence QY up to 18.7% at room temperature are obtained. After covalently attaching folic acid on the particle surface, tumor-specific nanoprobes are obtained for simultaneously visualizing both subcutaneous and intraperitoneal tumor xenografts in vivo. The ultrahigh QY of down-conversion emission also allows for visualization of the biodistribution of folate receptors.

[1]  Mingyuan Gao,et al.  Ultra-small nanocluster mediated synthesis of Nd3+-doped core-shell nanocrystals with emission in the second near-infrared window for multimodal imaging of tumor vasculature. , 2018, Biomaterials.

[2]  Mingyuan Gao,et al.  Coordinatively Unsaturated Fe3+ Based Activable Probes for Enhanced MRI and Therapy of Tumors. , 2019, Angewandte Chemie.

[3]  R. Prevedel,et al.  Aggregation-Induced Emission Luminogen with Near-Infrared-II Excitation and Near-Infrared-I Emission for Ultradeep Intravital Two-Photon Microscopy. , 2018, ACS nano.

[4]  Datao Tu,et al.  Intense near-infrared-II luminescence from NaCeF4:Er/Yb nanoprobes for in vitro bioassay and in vivo bioimaging , 2018, Chemical science.

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

[6]  G Toffoli,et al.  Overexpression of folate binding protein in ovarian cancers , 1997, International journal of cancer.

[7]  D. Fan,et al.  Confining Excitation Energy in Er3+ -Sensitized Upconversion Nanocrystals through Tm3+ -Mediated Transient Energy Trapping. , 2017, Angewandte Chemie.

[8]  J. G. Solé,et al.  1.3 μm emitting SrF2:Nd3+ nanoparticles for high contrast in vivo imaging in the second biological window , 2015, Nano Research.

[9]  M. C. Mancini,et al.  Bioimaging: second window for in vivo imaging. , 2009, Nature nanotechnology.

[10]  Ziqian Li,et al.  Detection of early primary colorectal cancer with upconversion luminescent NP-based molecular probes. , 2016, Nanoscale.

[11]  Fan Zhang,et al.  Lifetime-engineered NIR-II nanoparticles unlock multiplexed in vivo imaging , 2018, Nature Nanotechnology.

[12]  Junle Qu,et al.  Efficient Erbium‐Sensitized Core/Shell Nanocrystals for Short Wave Infrared Bioimaging , 2018, Advanced Optical Materials.

[13]  Datao Tu,et al.  Large-scale synthesis of uniform lanthanide-doped NaREF4 upconversion/downshifting nanoprobes for bioapplications. , 2018, Nanoscale.

[14]  Mingyuan Gao,et al.  Magnetic/upconversion fluorescent NaGdF4:Yb,Er nanoparticle-based dual-modal molecular probes for imaging tiny tumors in vivo. , 2013, ACS nano.

[15]  Mingyuan Gao,et al.  Detection of lymph node metastasis with near-infrared upconversion luminescent nanoprobes. , 2018, Nanoscale.

[16]  Yuxin Liu,et al.  Simultaneous Activation of Short‐Wave Infrared (SWIR) Light and Paramagnetism by a Functionalized Shell for High Penetration and Spatial Resolution Theranostics , 2018 .

[17]  H. Dai,et al.  Direct Evidence for Coupled Surface and Concentration Quenching Dynamics in Lanthanide-Doped Nanocrystals. , 2017, Journal of the American Chemical Society.

[18]  Noah D Bronstein,et al.  Precise Tuning of Surface Quenching for Luminescence Enhancement in Core-Shell Lanthanide-Doped Nanocrystals. , 2016, Nano letters.

[19]  Shuo Diao,et al.  Through-skull fluorescence imaging of the brain in a new near-infrared window , 2014, Nature Photonics.

[20]  Kezhi Zheng,et al.  Advances in highly doped upconversion nanoparticles , 2018, Nature Communications.

[21]  Wing-Cheung Law,et al.  Core/shell NaGdF4:Nd(3+)/NaGdF4 nanocrystals with efficient near-infrared to near-infrared downconversion photoluminescence for bioimaging applications. , 2012, ACS nano.

[22]  Xiaomin Liu,et al.  Excitation energy migration dynamics in upconversion nanomaterials. , 2015, Chemical Society reviews.

[23]  Juan Wang,et al.  Direct evidence of a surface quenching effect on size-dependent luminescence of upconversion nanoparticles. , 2010, Angewandte Chemie.

[24]  Qiangbin Wang,et al.  Facile Synthesis of Highly Photoluminescent Ag2Se Quantum Dots as a New Fluorescent Probe in the Second Near-Infrared Window for in Vivo Imaging , 2013 .

[25]  Mingyuan Gao,et al.  Ultrasensitive in vivo detection of primary gastric tumor and lymphatic metastasis using upconversion nanoparticles. , 2015, ACS nano.

[26]  Jianhua Hao,et al.  Non-Invasive Optical Guided Tumor Metastasis/Vessel Imaging by Using Lanthanide Nanoprobe with Enhanced Down-Shifting Emission beyond 1500 nm. , 2019, ACS nano.

[27]  P. Low,et al.  Immunohistochemical expression of folate receptor alpha in colorectal carcinoma: patterns and biological significance. , 2008, Human pathology.

[28]  F. Fang,et al.  NaGdF4 nanoparticle-based molecular probes for magnetic resonance imaging of intraperitoneal tumor xenografts in vivo. , 2013, ACS Nano.

[29]  Mingyuan Gao,et al.  Are Rare‐Earth Nanoparticles Suitable for In Vivo Applications? , 2014, Advanced materials.

[30]  J. Hao,et al.  A General In Situ Growth Strategy of Designing Theranostic NaLnF4@Cu2−xS Nanoplatform for In Vivo NIR‐II Optical Imaging Beyond 1500 nm and Photothermal Therapy , 2019, Advanced Therapeutics.

[31]  Mingyuan Gao,et al.  Differently sized magnetic/upconversion luminescent NaGdF4:Yb,Er nanocrystals: flow synthesis and solvent effects. , 2016, Chemical communications.

[32]  Qiangbin Wang,et al.  Challenges and Opportunities for Intravital Near-Infrared Fluorescence Imaging Technology in the Second Transparency Window. , 2018, ACS nano.

[33]  Restructuring and remodeling of NaREF4 nanocrystals by electron irradiation. , 2014, Small.

[34]  Mingyuan Gao,et al.  Biocompatible Semiconductor Quantum Dots as Cancer Imaging Agents , 2018, Advanced materials.

[35]  Zhuoran Ma,et al.  A bright organic NIR-II nanofluorophore for three-dimensional imaging into biological tissues , 2018, Nature Communications.

[36]  Shuo Diao,et al.  A small-molecule dye for NIR-II imaging. , 2016, Nature materials.

[37]  Ute Resch-Genger,et al.  Quantum Yields, Surface Quenching, and Passivation Efficiency for Ultrasmall Core/Shell Upconverting Nanoparticles. , 2018, Journal of the American Chemical Society.

[38]  H. Dai,et al.  Diagnosis of Zika virus infection on a nanotechnology platform , 2017, Nature Medicine.

[39]  R. Weissleder.  A clearer vision for in vivo imaging , 2001, Nature Biotechnology.

[40]  Helmut Schäfer,et al.  Upconverting nanoparticles. , 2011, Angewandte Chemie.

[41]  Oliver T. Bruns,et al.  Next-generation in vivo optical imaging with short-wave infrared quantum dots , 2017, Nature Biomedical Engineering.

[42]  Mingyuan Gao,et al.  Tumor Microenvironment‐Triggered Aggregation of Antiphagocytosis 99mTc‐Labeled Fe3O4 Nanoprobes for Enhanced Tumor Imaging In Vivo , 2017, Advanced materials.

[43]  B. Wall,et al.  Rare-earth-doped biological composites as in vivo shortwave infrared reporters , 2013, Nature Communications.

[44]  Guosong Hong,et al.  Multifunctional in vivo vascular imaging using near-infrared II fluorescence , 2012, Nature Medicine.

[45]  H. Dai,et al.  Biological imaging without autofluorescence in the second near-infrared region , 2015, Nano Research.

[46]  Jie Tian,et al.  Molecular Imaging of Vulnerable Atherosclerotic Plaques in Vivo with Osteopontin-Specific Upconversion Nanoprobes. , 2017, ACS nano.

[47]  Paul Kumar Upputuri,et al.  Compact Plasmonic Blackbody for Cancer Theranosis in the Near-Infrared II Window. , 2018, ACS nano.

[48]  Zhiyuan Hu,et al.  Boosting the down-shifting luminescence of rare-earth nanocrystals for biological imaging beyond 1500 nm , 2017, Nature Communications.

[49]  Shuo Diao,et al.  In vivo fluorescence imaging with Ag2S quantum dots in the second near-infrared region. , 2012, Angewandte Chemie.