skip to main content
DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: A high quantum yield molecule-protein complex fluorophore for near-infrared II imaging

Abstract

Fluorescence imaging in the second near-infrared window (NIR-II) allows visualization of deep anatomical features with an unprecedented degree of clarity. NIR-II fluorophores draw from a broad spectrum of materials spanning semiconducting nanomaterials to organic molecular dyes, yet unfortunately all water-soluble organic molecules with 41,000 nm emission suffer from low quantum yields that have limited temporal resolution and penetration depth. We report tailoring the supramolecular assemblies of protein complexes with a sulfonated NIR-II organic dye (CH-4T) to produce a brilliant 110-fold increase in fluorescence, resulting in the highest quantum yield molecular fluorophore thus far. The bright molecular complex allowed for the fastest video-rate imaging in the second NIR window with B50-fold reduced exposure times at a fast 50 frames-per-second (FPS) capable of resolving mouse cardiac cycles. Additionally, we demonstrate that the NIR-II molecular complexes are superior to clinically approved ICG for lymph node imaging deep within the mouse body.

Authors:
 [1];  [2];  [1];  [1];  [3];  [1];  [1];  [1];  [3]; ORCiD logo [1];  [3];  [3]; ORCiD logo [4];  [1];  [3]
  1. Stanford Univ., CA (United States). Dept. of Chemistry
  2. Wuhan Univ. (China). State Key Lab. of Virology, Key Lab. of Combinatorial Biosynthesis and Drug Discovery; Stanford Univ., CA (United States). Molecular Imaging Program (MIPS), Dept. of Radiology, Canary Center at Stanford for Cancer Early Detection
  3. Stanford Univ., CA (United States). Molecular Imaging Program (MIPS), Dept. of Radiology, Canary Center at Stanford for Cancer Early Detection
  4. Wuhan Univ. (China). State Key Lab. of Virology, Key Lab. of Combinatorial Biosynthesis and Drug Discovery
Publication Date:
Research Org.:
Stanford Univ., CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
OSTI Identifier:
1389584
Grant/Contract Number:  
SC0008397
Resource Type:
Accepted Manuscript
Journal Name:
Nature Communications
Additional Journal Information:
Journal Volume: 8; Journal ID: ISSN 2041-1723
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
36 MATERIALS SCIENCE; 60 APPLIED LIFE SCIENCES; biomedical materials; fluorescence imaging; supramolecular chemistry

Citation Formats

Antaris, Alexander L., Chen, Hao, Diao, Shuo, Ma, Zhuoran, Zhang, Zhe, Zhu, Shoujun, Wang, Joy, Lozano, Alexander X., Fan, Quli, Chew, Leila, Zhu, Mark, Cheng, Kai, Hong, Xuechuan, Dai, Hongjie, and Cheng, Zhen. A high quantum yield molecule-protein complex fluorophore for near-infrared II imaging. United States: N. p., 2017. Web. doi:10.1038/ncomms15269.
Antaris, Alexander L., Chen, Hao, Diao, Shuo, Ma, Zhuoran, Zhang, Zhe, Zhu, Shoujun, Wang, Joy, Lozano, Alexander X., Fan, Quli, Chew, Leila, Zhu, Mark, Cheng, Kai, Hong, Xuechuan, Dai, Hongjie, & Cheng, Zhen. A high quantum yield molecule-protein complex fluorophore for near-infrared II imaging. United States. doi:10.1038/ncomms15269.
Antaris, Alexander L., Chen, Hao, Diao, Shuo, Ma, Zhuoran, Zhang, Zhe, Zhu, Shoujun, Wang, Joy, Lozano, Alexander X., Fan, Quli, Chew, Leila, Zhu, Mark, Cheng, Kai, Hong, Xuechuan, Dai, Hongjie, and Cheng, Zhen. Fri . "A high quantum yield molecule-protein complex fluorophore for near-infrared II imaging". United States. doi:10.1038/ncomms15269. https://www.osti.gov/servlets/purl/1389584.
@article{osti_1389584,
title = {A high quantum yield molecule-protein complex fluorophore for near-infrared II imaging},
author = {Antaris, Alexander L. and Chen, Hao and Diao, Shuo and Ma, Zhuoran and Zhang, Zhe and Zhu, Shoujun and Wang, Joy and Lozano, Alexander X. and Fan, Quli and Chew, Leila and Zhu, Mark and Cheng, Kai and Hong, Xuechuan and Dai, Hongjie and Cheng, Zhen},
abstractNote = {Fluorescence imaging in the second near-infrared window (NIR-II) allows visualization of deep anatomical features with an unprecedented degree of clarity. NIR-II fluorophores draw from a broad spectrum of materials spanning semiconducting nanomaterials to organic molecular dyes, yet unfortunately all water-soluble organic molecules with 41,000 nm emission suffer from low quantum yields that have limited temporal resolution and penetration depth. We report tailoring the supramolecular assemblies of protein complexes with a sulfonated NIR-II organic dye (CH-4T) to produce a brilliant 110-fold increase in fluorescence, resulting in the highest quantum yield molecular fluorophore thus far. The bright molecular complex allowed for the fastest video-rate imaging in the second NIR window with B50-fold reduced exposure times at a fast 50 frames-per-second (FPS) capable of resolving mouse cardiac cycles. Additionally, we demonstrate that the NIR-II molecular complexes are superior to clinically approved ICG for lymph node imaging deep within the mouse body.},
doi = {10.1038/ncomms15269},
journal = {Nature Communications},
number = ,
volume = 8,
place = {United States},
year = {2017},
month = {5}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record

Citation Metrics:
Cited by: 64 works
Citation information provided by
Web of Science

Save / Share:

Works referenced in this record:

Lifetime, photostability, and chemical structure of IR heptamethine cyanine dyes absorbing beyond 1 ?m
journal, September 1982

  • Kopainsky, B.; Qiu, P.; Kaiser, W.
  • Applied Physics B Photophysics and Laser Chemistry, Vol. 29, Issue 1
  • DOI: 10.1007/BF00694363

Indocyanine Green: Physicochemical Factors Affecting Its Fluorescencein Vivo
journal, March 1998

  • Mordon, Serge; Devoisselle, Jean Marie; Soulie-Begu, Sylvie
  • Microvascular Research, Vol. 55, Issue 2
  • DOI: 10.1006/mvre.1998.2068

A TICT based NIR-fluorescent probe for human serum albumin: a pre-clinical diagnosis in blood serum
journal, January 2016

  • Reja, Shahi Imam; Khan, Imran A.; Bhalla, Vandana
  • Chemical Communications, Vol. 52, Issue 6
  • DOI: 10.1039/C5CC08217J

Fluorescence properties of indocyanine green as related to angiography
journal, January 1978


Photoacoustic imaging and characterization of the microvasculature
journal, January 2010

  • Hu, Song; Wang, Lihong V.
  • Journal of Biomedical Optics, Vol. 15, Issue 1
  • DOI: 10.1117/1.3281673

Efficient Fluorescence Enhancement and Cooperative Binding of an Organic Dye in a Supra-biomolecular Host–Protein Assembly
journal, May 2007

  • Bhasikuttan, Achikanath C.; Mohanty, Jyotirmayee; Nau, Werner M.
  • Angewandte Chemie International Edition, Vol. 46, Issue 22
  • DOI: 10.1002/anie.200604757

Carbon nanotubes as in vivo bacterial probes
journal, September 2014

  • Bardhan, Neelkanth M.; Ghosh, Debadyuti; Belcher, Angela M.
  • Nature Communications, Vol. 5, Issue 1
  • DOI: 10.1038/ncomms5918

Fluorescence Properties and Metabolic Features of Indocyanine Green (ICG) as Related to Angiography
journal, July 2000


Laser Speckle Contrast Imaging: Theory, Instrumentation and Applications
journal, January 2013


Near-Infrared II Fluorescence for Imaging Hindlimb Vessel Regeneration With Dynamic Tissue Perfusion Measurement
journal, May 2014


Fluorescence Imaging In Vivo at Wavelengths beyond 1500 nm
journal, October 2015

  • Diao, Shuo; Blackburn, Jeffrey L.; Hong, Guosong
  • Angewandte Chemie International Edition, Vol. 54, Issue 49
  • DOI: 10.1002/anie.201507473

Absolute Photoluminescence Quantum Yields of IR-26 Dye, PbS, and PbSe Quantum Dots
journal, July 2010

  • Semonin, Octavi E.; Johnson, Justin C.; Luther, Joseph M.
  • The Journal of Physical Chemistry Letters, Vol. 1, Issue 16
  • DOI: 10.1021/jz100830r

Layer-by-layer assembled fluorescent probes in the second near-infrared window for systemic delivery and detection of ovarian cancer
journal, April 2016

  • Dang, Xiangnan; Gu, Li; Qi, Jifa
  • Proceedings of the National Academy of Sciences, Vol. 113, Issue 19
  • DOI: 10.1073/pnas.1521175113

Deep optical imaging of tissue using the second and third near-infrared spectral windows
journal, May 2014

  • Sordillo, Laura A.; Pu, Yang; Pratavieira, Sebastião
  • Journal of Biomedical Optics, Vol. 19, Issue 5
  • DOI: 10.1117/1.JBO.19.5.056004

Randomized, double-blind comparison of indocyanine green with or without albumin premixing for near-infrared fluorescence imaging of sentinel lymph nodes in breast cancer patients
journal, March 2011

  • Hutteman, Merlijn; Mieog, J. Sven D.; van der Vorst, Joost R.
  • Breast Cancer Research and Treatment, Vol. 127, Issue 1
  • DOI: 10.1007/s10549-011-1419-0

Through-skull fluorescence imaging of the brain in a new near-infrared window
journal, August 2014


Chirality Enriched (12,1) and (11,3) Single-Walled Carbon Nanotubes for Biological Imaging
journal, October 2012

  • Diao, Shuo; Hong, Guosong; Robinson, Joshua T.
  • Journal of the American Chemical Society, Vol. 134, Issue 41
  • DOI: 10.1021/ja307966u

A small-molecule dye for NIR-II imaging
journal, November 2015

  • Antaris, Alexander L.; Chen, Hao; Cheng, Kai
  • Nature Materials, Vol. 15, Issue 2
  • DOI: 10.1038/nmat4476

M13 Phage-Functionalized Single-Walled Carbon Nanotubes As Nanoprobes for Second Near-Infrared Window Fluorescence Imaging of Targeted Tumors
journal, February 2012

  • Yi, Hyunjung; Ghosh, Debadyuti; Ham, Moon-Ho
  • Nano Letters, Vol. 12, Issue 3
  • DOI: 10.1021/nl2031663

Biological Imaging Using Nanoparticles of Small Organic Molecules with Fluorescence Emission at Wavelengths Longer than 1000 nm
journal, October 2013

  • Tao, Zhimin; Hong, Guosong; Shinji, Chihiro
  • Angewandte Chemie International Edition, Vol. 52, Issue 49
  • DOI: 10.1002/anie.201307346

PbTe Colloidal Nanocrystals:  Synthesis, Characterization, and Multiple Exciton Generation
journal, March 2006

  • Murphy, James E.; Beard, Matthew C.; Norman, Andrew G.
  • Journal of the American Chemical Society, Vol. 128, Issue 10
  • DOI: 10.1021/ja0574973

Deep, noninvasive imaging and surgical guidance of submillimeter tumors using targeted M13-stabilized single-walled carbon nanotubes
journal, September 2014

  • Ghosh, D.; Bagley, A. F.; Na, Y. J.
  • Proceedings of the National Academy of Sciences, Vol. 111, Issue 38
  • DOI: 10.1073/pnas.1400821111

In vivo biosensing via tissue-localizable near-infrared-fluorescent single-walled carbon nanotubes
journal, November 2013

  • Iverson, Nicole M.; Barone, Paul W.; Shandell, Mia
  • Nature Nanotechnology, Vol. 8, Issue 11
  • DOI: 10.1038/nnano.2013.222

A route to brightly fluorescent carbon nanotubes for near-infrared imaging in mice
journal, October 2009

  • Welsher, Kevin; Liu, Zhuang; Sherlock, Sarah P.
  • Nature Nanotechnology, Vol. 4, Issue 11
  • DOI: 10.1038/nnano.2009.294

Targeted zwitterionic near-infrared fluorophores for improved optical imaging
journal, January 2013

  • Choi, Hak Soo; Gibbs, Summer L.; Lee, Jeong Heon
  • Nature Biotechnology, Vol. 31, Issue 2
  • DOI: 10.1038/nbt.2468

Novel benzo-bis(1,2,5-thiadiazole) fluorophores for in vivo NIR-II imaging of cancer
journal, January 2016

  • Sun, Yao; Qu, Chunrong; Chen, Hao
  • Chemical Science, Vol. 7, Issue 9
  • DOI: 10.1039/C6SC01561A

Considerable fluorescence enhancement upon supramolecular complex formation between berberine and p-sulfonated calixarenes
journal, June 2006


Bright, Color-Tunable Fluorescent Dyes in the Visible−Near-Infrared Region
journal, February 2008

  • Umezawa, Keitaro; Nakamura, Yuki; Makino, Hiroshi
  • Journal of the American Chemical Society, Vol. 130, Issue 5
  • DOI: 10.1021/ja077756j

Use of laser speckle flowgraphy in ocular blood flow research
journal, September 2009


Optimization of near-infrared fluorescent sentinel lymph node mapping for vulvar cancer
journal, January 2012

  • Hutteman, Merlijn; van der Vorst, Joost R.; Gaarenstroom, Katja N.
  • American Journal of Obstetrics and Gynecology, Vol. 206, Issue 1
  • DOI: 10.1016/j.ajog.2011.07.039

Synthesis and In Vivo Fate of Zwitterionic Near-Infrared Fluorophores
journal, June 2011

  • Choi, Hak Soo; Nasr, Khaled; Alyabyev, Sergey
  • Angewandte Chemie International Edition, Vol. 50, Issue 28
  • DOI: 10.1002/anie.201102459

Multifunctional in vivo vascular imaging using near-infrared II fluorescence
journal, November 2012

  • Hong, Guosong; Lee, Jerry C.; Robinson, Joshua T.
  • Nature Medicine, Vol. 18, Issue 12
  • DOI: 10.1038/nm.2995

Recent advances in twisted intramolecular charge transfer (TICT) fluorescence and related phenomena in materials chemistry
journal, January 2016

  • Sasaki, Shunsuke; Drummen, Gregor P. C.; Konishi, Gen-ichi
  • Journal of Materials Chemistry C, Vol. 4, Issue 14
  • DOI: 10.1039/C5TC03933A

Traumatic Brain Injury Imaging in the Second Near-Infrared Window with a Molecular Fluorophore
journal, June 2016

  • Zhang, Xiao-Dong; Wang, Huasen; Antaris, Alexander L.
  • Advanced Materials, Vol. 28, Issue 32
  • DOI: 10.1002/adma.201600706

Stabilization of Indocyanine Green by Encapsulation within Micellar Systems
journal, February 2009

  • Kirchherr, Anne-Katrin; Briel, Andreas; Mäder, Karsten
  • Molecular Pharmaceutics, Vol. 6, Issue 2
  • DOI: 10.1021/mp8001649

Sedimentation equilibrium of proteins in density gradients
journal, July 1976


Photophysical and photochemical switches based on twisted intramolecular charge transfer (TICT) states
journal, March 1988

  • Rettig, W.
  • Applied Physics B Photophysics and Laser Chemistry, Vol. 45, Issue 3
  • DOI: 10.1007/BF00695283

Ultrafast fluorescence imaging in vivo with conjugated polymer fluorophores in the second near-infrared window
journal, June 2014

  • Hong, Guosong; Zou, Yingping; Antaris, Alexander L.
  • Nature Communications, Vol. 5, Issue 1
  • DOI: 10.1038/ncomms5206

    Works referencing / citing this record:

    NIR-II Fluorescence Imaging of Skin Avulsion and Necrosis
    journal, October 2019


    Diaminodicyanoquinones: Fluorescent Dyes with High Dipole Moments and Electron-Acceptor Properties
    journal, May 2019

    • Rietsch, Philipp; Witte, Felix; Sobottka, Sebastian
    • Angewandte Chemie International Edition, Vol. 58, Issue 24
    • DOI: 10.1002/anie.201903204

    Molecular Cancer Imaging in the Second Near-Infrared Window Using a Renal-Excreted NIR-II Fluorophore-Peptide Probe
    journal, April 2018


    Diaminodicyanoquinones: Fluorescent Dyes with High Dipole Moments and Electron-Acceptor Properties
    journal, May 2019

    • Rietsch, Philipp; Witte, Felix; Sobottka, Sebastian
    • Angewandte Chemie International Edition, Vol. 58, Issue 24
    • DOI: 10.1002/anie.201903204

    NIR-II Fluorescence Imaging of Skin Avulsion and Necrosis
    journal, October 2019