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In vivo NIR-II fluorescence imaging for biology and medicine

Nature Photonics (2024)Cite this article

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Abstract

Owing to reduced light scattering and tissue autofluorescence, in vivo fluorescence imaging in the 1,000–3,000-nm near-infrared II (NIR-II) spectral range can afford non-invasive imaging at depths of millimetres within biological tissue. Infrared fluorescent probes labelled with antibodies or other targeting ligands also enable NIR-II molecular imaging at the single-cell level. Here we present recent developments in the design of fluorophores and probes emitting in the NIR-II window based on organic synthesis and nanoscience approaches. We also review advances in NIR-II wide-field and microscopy imaging modalities, with a focus on preclinical imaging and promising clinical translation case studies. Finally, we outline current issues and challenges for the wider adoption of NIR-II imaging in biomedical research and clinical imaging.

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Fig. 1: Motivation for NIR-II fluorescence imaging.
Fig. 2: NIR-II fluorescence probes.
Fig. 3: NIR-II imaging modalities.
Fig. 4: NIR-II preclinical imaging.
Fig. 5: NIR-II clinical imaging.

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References

  1. Genack, A. Z., Chabanov, A. A., Sebbah, P. & van Tiggelen, B. A. in Encyclopedia of Condensed Matter Physics (eds Bassani, F., Liedl, G. L. & Wyder, P.) 307–317 (Elsevier, 2005).

  2. Shi, L. & Alfano, R. R. Deep Imaging in Tissue and Biomedical Materials: using Linear and Nonlinear Optical Methods (CRC Press, 2017).

  3. Jacques, S. L. Optical properties of biological tissues: a review. Phys. Med. Biol. 58, R37–R61 (2013).

    Article  Google Scholar 

  4. Hong, G., Antaris, A. L. & Dai, H. Near-infrared fluorophores for biomedical imaging. Nat. Biomed. Eng. 1, 0010 (2017).

    Article  CAS  Google Scholar 

  5. Hong, G. et al. Through-skull fluorescence imaging of the brain in a new near-infrared window. Nat. Photon. 8, 723–730 (2014).

    Article  ADS  CAS  Google Scholar 

  6. Weissleder, R. A clearer vision for in vivo imaging. Nat. Biotechnol. 19, 316–317 (2001).

    Article  CAS  PubMed  Google Scholar 

  7. Friebel, M., Helfmann, J., Netz, U. & Meinke, M. Influence of oxygen saturation on the optical scattering properties of human red blood cells in the spectral range 250 to 2,000 nm. J. Biomed. Opt. 14, 034001 (2009).

    Article  ADS  PubMed  Google Scholar 

  8. Reinhart, M. B., Huntington, C. R., Blair, L. J., Heniford, B. T. & Augenstein, V. A. Indocyanine green: historical context, current applications and future considerations. Surg. Innov. 23, 166–175 (2016).

    Article  PubMed  Google Scholar 

  9. Smith, A. M., Mancini, M. C. & Nie, S. Second window for in vivo imaging. Nat. Nanotechnol. 4, 710–711 (2009).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  10. Diao, S. et al. Biological imaging without autofluorescence in the second near-infrared region. Nano Res. 8, 3027–3034 (2015).

    Article  CAS  Google Scholar 

  11. Welsher, K. et al. A route to brightly fluorescent carbon nanotubes for near-infrared imaging in mice. Nat. Nanotechnol. 4, 773–780 (2009).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  12. Wang, F. et al. In vivo non-invasive confocal fluorescence imaging beyond 1,700 nm using superconducting nanowire single-photon detectors. Nat. Nanotechnol. 17, 653–660 (2022).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  13. Liu, Z., Tabakman, S., Welsher, K. & Dai, H. Carbon nanotubes in biology and medicine: in vitro and in vivo detection, imaging and drug delivery. Nano Res. 2, 85–120 (2009).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  14. Welsher, K., Sherlock, S. P. & Dai, H. Deep-tissue anatomical imaging of mice using carbon nanotube fluorophores in the second near-infrared window. Proc. Natl Acad. Sci. USA 108, 8943–8948 (2011).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  15. Hong, G. et al. Multifunctional in vivo vascular imaging using near-infrared II fluorescence. Nat. Med. 18, 1841–1846 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Hong, G. et al. In vivo fluorescence imaging with Ag2S quantum dots in the second near-infrared region. Angew. Chem. Int. Edit. 51, 9818–9821 (2012).

    Article  CAS  Google Scholar 

  17. Diao, S. et al. Fluorescence imaging in vivo at wavelengths beyond 1,500 nm. Angew. Chem. Int. Ed. 54, 14758–14762 (2015).

    Article  CAS  Google Scholar 

  18. Antaris, A. L. et al. A small-molecule dye for NIR-II imaging. Nat. Mater. 15, 235–242 (2016).

    Article  ADS  CAS  PubMed  Google Scholar 

  19. Zhong, Y. et al. Boosting the down-shifting luminescence of rare-earth nanocrystals for biological imaging beyond 1,500 nm. Nat. Commun. 8, 737 (2017).

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  20. Wan, H. et al. Developing a bright NIR-II fluorophore with fast renal excretion and its application in molecular imaging of immune checkpoint PD-L1. Adv. Funct. Mater. 28, 1804956 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  21. Zhang, M. et al. Bright quantum dots emitting at ∼1,600 nm in the NIR-IIb window for deep tissue fluorescence imaging. Proc. Natl Acad. Sci. USA 115, 6590–6595 (2018).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  22. Ma, Z. et al. A theranostic agent for cancer therapy and imaging in the second near-infrared window. Nano Res. 12, 273–279 (2019).

    Article  PubMed  Google Scholar 

  23. Zhong, Y. et al. In vivo molecular imaging for immunotherapy using ultra-bright near-infrared-IIb rare-earth nanoparticles. Nat. Biotechnol. 37, 1322–1331 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Wang, F. et al. Light-sheet microscopy in the near-infrared II window. Nat. Methods 16, 545–552 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  25. Ma, Z. et al. Cross-link-functionalized nanoparticles for rapid excretion in nanotheranostic applications. Angew. Chem. Int. Ed. 59, 20552–20560 (2020).

    Article  CAS  Google Scholar 

  26. Wang, F. et al. In vivo NIR-II structured-illumination light-sheet microscopy. Proc. Natl Acad. Sci. USA 118, e2023888118 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Baghdasaryan, A. et al. Phosphorylcholine-conjugated gold-molecular clusters improve signal for lymph node NIR-II fluorescence imaging in preclinical cancer models. Nat. Commun. 13, 5613 (2022).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  28. Wang, F. et al. High-precision tumor resection down to few-cell level guided by NIR-IIb molecular fluorescence imaging. Proc. Natl Acad. Sci. USA 119, e2123111119 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Ren, F. et al. Shortwave-infrared-light-emitting probes for the in vivo tracking of cancer vaccines and the elicited immune responses. Nat. Biomed. Eng. (2023); https://doi.org/10.1038/s41551-023-01083-5

  30. Carr, J. A. et al. Absorption by water increases fluorescence image contrast of biological tissue in the shortwave infrared. Proc. Natl Acad. Sci. USA 115, 9080–9085 (2018).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  31. Yoo, K. M., Liu, F. & Alfano, R. R. Imaging through a scattering wall using absorption. Opt. Lett. 16, 1068–1070 (1991).

    Article  ADS  CAS  PubMed  Google Scholar 

  32. Shao, W. et al. Tunable narrow band emissions from dye-sensitized core/shell/shell nanocrystals in the second near-infrared biological window. J. Am. Chem. Soc. 138, 16192–16195 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Wei, Y.-C. et al. Overcoming the energy gap law in near-infrared OLEDs by exciton–vibration decoupling. Nat. Photon. 14, 570–577 (2020).

    Article  ADS  CAS  Google Scholar 

  34. Zhu, S., Tian, R., Antaris, A. L., Chen, X. & Dai, H. Near-infrared-II molecular dyes for cancer imaging and surgery. Adv. Mater. 31, 1900321 (2019).

    Article  Google Scholar 

  35. Chen, R. J., Zhang, Y., Wang, D. & Dai, H. Noncovalent sidewall functionalization of single-walled carbon nanotubes for protein immobilization. J. Am. Chem. Soc. 123, 3838–3839 (2001).

    Article  CAS  PubMed  Google Scholar 

  36. Zhang, Y. et al. Ag2S quantum dot: a bright and biocompatible fluorescent nanoprobe in the second near-infrared window. ACS Nano 6, 3695–3702 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Bruns, O. T. et al. Next-generation in vivo optical imaging with short-wave infrared quantum dots. Nat. Biomed. Eng. 1, 0056 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Pei, P. et al. X-ray-activated persistent luminescence nanomaterials for NIR-II imaging. Nat. Nanotechnol. 16, 1011–1018 (2021).

    Article  ADS  CAS  PubMed  Google Scholar 

  39. Zhong, Y. & Dai, H. A mini-review on rare-earth down-conversion nanoparticles for NIR-II imaging of biological systems. Nano Res. 13, 1281–1294 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Gu, Y. et al. High-sensitivity imaging of time-domain near-infrared light transducer. Nat. Photon. 13, 525–531 (2019).

    Article  ADS  CAS  Google Scholar 

  41. Yang, Y. et al. Fluorescence-amplified nanocrystals in the second near-infrared window for in vivo real-time dynamic multiplexed imaging. Nat. Nanotechnol. 18, 1195–1204 (2023).

    Article  ADS  CAS  PubMed  Google Scholar 

  42. Chen, Y. et al. Shortwave infrared in vivo imaging with gold nanoclusters. Nano Lett. 17, 6330–6334 (2017).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  43. Ma, H. et al. Bioactive NIR-II gold clusters for three-dimensional imaging and acute inflammation inhibition. Sci. Adv. 9, eadh7828 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Cosco, E. D. et al. Shortwave infrared polymethine fluorophores matched to excitation lasers enable non-invasive, multicolour in vivo imaging in real time. Nat. Chem. 12, 1123–1130 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Sun, C. et al. J-aggregates of cyanine dye for NIR-II in vivo dynamic vascular imaging beyond 1,500 nm. J. Am. Chem. Soc. 141, 19221–19225 (2019).

    Article  CAS  PubMed  Google Scholar 

  46. Yang, Q. et al. Rational design of molecular fluorophores for biological imaging in the NIR-II window. Adv. Mater. 29, 1605497 (2017).

    Article  Google Scholar 

  47. Zhu, X. et al. High brightness NIR-II nanofluorophores based on fused-ring acceptor molecules. Nano Res. 13, 2570–2575 (2020).

    Article  CAS  Google Scholar 

  48. Yao, C. et al. A bright, renal-clearable NIR-II brush macromolecular probe with long blood circulation time for kidney disease bioimaging. Angew. Chem. Int. Ed. 61, e202114273 (2022).

    Article  ADS  CAS  Google Scholar 

  49. Qin, Z. et al. NIRII-HDs: a versatile platform for developing activatable NIR-II fluorogenic probes for reliable in vivo analyte sensing. Angew. Chem. Int. Ed. 61, e202201541 (2022).

    Article  ADS  CAS  Google Scholar 

  50. Wang, T. et al. A hybrid erbium(III)–bacteriochlorin near-infrared probe for multiplexed biomedical imaging. Nat. Mater. 20, 1571–1578 (2021).

    Article  ADS  CAS  PubMed  Google Scholar 

  51. Lei, Z. et al. Stable, wavelength-tunable fluorescent dyes in the NIR-II region for in vivo high-contrast bioimaging and multiplexed biosensing. Angew. Chem. Int. Ed. 58, 8166–8171 (2019).

    Article  CAS  Google Scholar 

  52. Liu, S. et al. Incorporation of planar blocks into twisted skeletons: boosting brightness of fluorophores for bioimaging beyond 1,500 nanometer. ACS Nano 14, 14228–14239 (2020).

    Article  CAS  PubMed  Google Scholar 

  53. Liu, C. et al. 3,4-Ethylenedithio thiophene donor for NIR-II fluorophores with improved quantum yields. Mater. Chem. Front. 7, 2419–2425 (2023).

    Article  ADS  CAS  Google Scholar 

  54. Ma, H. et al. Propylenedioxy thiophene donor to achieve NIR-II molecular fluorophores with enhanced brightness. Chem. Mater. 32, 2061–2069 (2020).

    Article  CAS  Google Scholar 

  55. Yang, Q. et al. Donor engineering for NIR-II molecular fluorophores with enhanced fluorescent performance. J. Am. Chem. Soc. 140, 1715–1724 (2018).

    Article  CAS  PubMed  Google Scholar 

  56. Huang, J. et al. Renal-clearable molecular semiconductor for second near-infrared fluorescence imaging of kidney dysfunction. Angew. Chem. Int. Ed. 58, 15120–15127 (2019).

    Article  CAS  Google Scholar 

  57. Shcherbakova, D. M. & Verkhusha, V. V. Near-infrared fluorescent proteins for multicolor in vivo imaging. Nat. Methods 10, 751–754 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Oliinyk, O. S., Chernov, K. G. & Verkhusha, V. V. Bacterial phytochromes, cyanobacteriochromes and allophycocyanins as a source of near-infrared fluorescent probes. Int. J. Mol. Sci. 18, 1691 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  59. Chen, M. et al. Long-term monitoring of intravital biological processes using fluorescent protein-assisted NIR-II imaging. Nat. Commun. 13, 6643 (2022).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  60. Oliinyk, O. S. et al. Deep-tissue SWIR imaging using rationally designed small red-shifted near-infrared fluorescent protein. Nat. Methods 20, 70–74 (2023).

    Article  CAS  PubMed  Google Scholar 

  61. Naczynski, D. J. et al. X-ray-induced shortwave infrared biomedical imaging using rare-earth nanoprobes. Nano Lett. 15, 96–102 (2015).

    Article  ADS  CAS  PubMed  Google Scholar 

  62. Cao, X. et al. Cherenkov excited short-wavelength infrared fluorescence imaging in vivo with external beam radiation. J. Biomed. Opt. 24, 051405 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  63. Shen, H. et al. Rational design of NIR-II AIEgens with ultrahigh quantum yields for photo- and chemiluminescence imaging. J. Am. Chem. Soc. 144, 15391–15402 (2022).

    Article  CAS  PubMed  Google Scholar 

  64. Lu, L. et al. NIR-II bioluminescence for in vivo high contrast imaging and in situ ATP-mediated metastases tracing. Nat. Commun. 11, 4192 (2020).

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  65. Wang, S. et al. Anti-quenching NIR-II molecular fluorophores for in vivo high-contrast imaging and pH sensing. Nat. Commun. 10, 1058 (2019).

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  66. Starosolski, Z. et al. Indocyanine green fluorescence in second near-infrared (NIR-II) window. PLoS ONE 12, e0187563 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  67. Ren, T.-B. et al. A general strategy for development of activatable NIR-II fluorescent probes for in vivo high-contrast bioimaging. Angew. Chem. Int. Ed. 60, 800–805 (2021).

    Article  ADS  CAS  Google Scholar 

  68. Wang, Z. et al. Dynamically monitoring lymphatic and vascular systems in physiological and pathological conditions of a swine model via a portable NIR-II imaging system with ICG. Int. J. Med. Sci. 19, 1864–1874 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Xue, D. et al. Structural and functional NIR-II fluorescence bioimaging in urinary system via clinically approved dye methylene blue. Engineering 22, 149–158 (2023).

    Article  CAS  Google Scholar 

  70. Chang, Y. et al. Bright Tm3+-based downshifting luminescence nanoprobe operating around 1,800 nm for NIR-IIb and c bioimaging. Nat. Commun. 14, 1079 (2023).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  71. Arús, B. A. et al. Shortwave infrared fluorescence imaging of peripheral organs in awake and freely moving mice. Front. Neurosci 17, 1135494 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  72. Kim, T., O’Brien, C., Choi, H. S. & Jeong, M. Y. Fluorescence molecular imaging systems for intraoperative image-guided surgery. Appl. Spectrosc. Rev. 53, 349–359 (2018).

    Article  ADS  Google Scholar 

  73. Wan, H. et al. A bright organic NIR-II nanofluorophore for three-dimensional imaging into biological tissues. Nat. Commun. 9, 1171 (2018).

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  74. Yu, W. et al. NIR-II fluorescence in vivo confocal microscopy with aggregation-induced emission dots. Sci. Bull. 64, 410–416 (2019).

    Article  CAS  Google Scholar 

  75. Yu, J. et al. Intravital confocal fluorescence lifetime imaging microscopy in the second near-infrared window. Opt. Lett. 45, 3305–3308 (2020).

    Article  ADS  PubMed  Google Scholar 

  76. Xia, F. et al. Short-wave infrared confocal fluorescence imaging of deep mouse brain with a superconducting nanowire single-photon detector. ACS Photon. 8, 2800–2810 (2021).

    Article  CAS  Google Scholar 

  77. Kobat, D., Horton, N. & Xu, C. In vivo two-photon microscopy to 1.6-mm depth in mouse cortex. J. Biomed. Opt. 16, 106014 (2011).

    Article  ADS  PubMed  Google Scholar 

  78. Horton, N. G. et al. In vivo three-photon microscopy of subcortical structures within an intact mouse brain. Nat. Photon. 7, 205–209 (2013).

    Article  ADS  CAS  Google Scholar 

  79. Gu, M., Gan, X., Kisteman, A. & Xu, M. G. Comparison of penetration depth between two-photon excitation and single-photon excitation in imaging through turbid tissue media. Appl. Phys. Lett. 77, 1551–1553 (2000).

    Article  ADS  CAS  Google Scholar 

  80. Huisken, J., Swoger, J., Del Bene, F., Wittbrodt, J. & Stelzer, E. H. K. Optical sectioning deep inside live embryos by selective plane illumination microscopy. Science 305, 1007–1009 (2004).

    Article  ADS  CAS  PubMed  Google Scholar 

  81. Liu, T.-L. et al. Observing the cell in its native state: imaging subcellular dynamics in multicellular organisms. Science 360, eaaq1392 (2018).

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  82. Yu, H. et al. Combining near-infrared excitation with Swept Confocally-Aligned Planar Excitation (SCAPE) microscopy for fast, volumetric imaging in mouse brain. In Biophotonics Congress: Biomedical Optics Congress 2018 (Microscopy/Translational/Brain/OTS). BF3C.3 (Optica Publishing Group, 2018).

  83. Olarte, O. E. et al. Image formation by linear and nonlinear digital scanned light-sheet fluorescence microscopy with Gaussian and Bessel beam profiles. Biomed. Opt. Express 3, 1492–1505 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  84. Nylk, J. et al. Light-sheet microscopy with attenuation-compensated propagation-invariant beams. Sci. Adv. 4, eaar4817 (2018).

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  85. Herisson, F. et al. Direct vascular channels connect skull bone marrow and the brain surface enabling myeloid cell migration. Nat. Neurosci. 21, 1209–1217 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Wang, F. et al. Scanning superlens microscopy for non-invasive large field-of-view visible light nanoscale imaging. Nat. Commun. 7, 13748 (2016).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  87. Liu, P. et al. Airy beam assisted NIR-II light-sheet microscopy. Nano Today 47, 101628 (2022).

    Article  CAS  Google Scholar 

  88. Gustafsson, M. G. L. Nonlinear structured-illumination microscopy: wide-field fluorescence imaging with theoretically unlimited resolution. Proc. Natl Acad. Sci. USA 102, 13081–13086 (2005).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  89. Hong, G. et al. Near-Infrared II fluorescence for imaging hindlimb vessel regeneration with dynamic tissue perfusion measurement. Circ. Cardiovasc. Imag. 7, 517–525 (2014).

    Article  Google Scholar 

  90. Qi, J. et al. Real-time and high-resolution bioimaging with bright aggregation-induced emission dots in short-wave infrared region. Adv. Mater. 30, 1706856 (2018).

    Article  Google Scholar 

  91. Liu, H. et al. Atomic-precision gold clusters for NIR-II imaging. Adv. Mater. 31, 1901015 (2019).

    Article  CAS  Google Scholar 

  92. Zhang, X.-D. et al. Traumatic brain injury imaging in the second near-infrared window with a molecular fluorophore. Adv. Mater. 28, 6872–6879 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Chatterjee, A., Serniak, N. & Czerniecki, B. J. Sentinel lymph node biopsy in breast cancer: a work in progress. Cancer J. 21, 7–10 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  94. Tian, R. et al. Multiplexed NIR-II probes for lymph node-invaded cancer detection and imaging-guided surgery. Adv. Mater. 32, 1907365 (2020).

    Article  CAS  Google Scholar 

  95. Li, M. et al. Near-infrared-II ratiometric fluorescence probes for non-invasive detection and precise navigation surgery of metastatic sentinel lymph nodes. Theranostics 12, 7191–7202 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Hu, Z. et al. First-in-human liver-tumour surgery guided by multispectral fluorescence imaging in the visible and near-infrared-I/II windows. Nat. Biomed. Eng. 4, 259–271 (2020).

    Article  PubMed  Google Scholar 

  97. Morlandt, A. B. et al. Fluorescently labeled Cetuximab-IRDye800 for guided surgical excision of ameloblastoma: a proof of principle study. J. Oral. Maxil. Surg. 78, 1736–1747 (2020).

    Article  Google Scholar 

  98. Suo, Y. et al. NIR-II fluorescence endoscopy for targeted imaging of colorectal cancer. Adv. Healthc. Mater. 8, 1900974 (2019).

    Article  CAS  Google Scholar 

  99. Girard, J.-P., Moussion, C. & Förster, R. HEVs, lymphatics and homeostatic immune cell trafficking in lymph nodes. Nat. Rev. Immunol. 12, 762–773 (2012).

    Article  CAS  PubMed  Google Scholar 

  100. He, L. et al. Engineering of reversible NIR-II redox-responsive fluorescent probes for imaging of inflammation in vivo. Angew. Chem. Int. Ed. 61, e202211409 (2022).

    Article  CAS  Google Scholar 

  101. Lan, Q. et al. Polymethine molecular platform for ratiometric fluorescent probes in the second near-infrared window. J. Am. Chem. Soc. 144, 21010–21015 (2022).

    Article  CAS  PubMed  Google Scholar 

  102. Miao, J. et al. An activatable NIR-II fluorescent reporter for in vivo imaging of amyloid-β plaques. Angew. Chem. Int. Ed. 62, e202216351 (2023).

    Article  CAS  Google Scholar 

  103. He, Y. et al. NIR-II cell endocytosis-activated fluorescent probes for in vivo high-contrast bioimaging diagnostics. Chem. Sci. 12, 10474–10482 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Chen, Z. et al. Design and synthesis of a small molecular NIR-II chemiluminescence probe for in vivo-activated H2S imaging. Proc. Natl Acad. Sci. USA 120, e2205186120 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Fang, Z. et al. Oxyhaemoglobin saturation NIR-IIb imaging for assessing cancer metabolism and predicting the response to immunotherapy. Nat. Nanotechnol 19, 124–130 (2024).

    Article  ADS  CAS  PubMed  Google Scholar 

  106. Tian, R. et al. Rational design of a super-contrast NIR-II fluorophore affords high-performance NIR-II molecular imaging guided microsurgery. Chem. Sci. 10, 326–332 (2019).

    Article  CAS  PubMed  Google Scholar 

  107. Wang, P. et al. NIR-II nanoprobes in-vivo assembly to improve image-guided surgery for metastatic ovarian cancer. Nat. Commun. 9, 2898 (2018).

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  108. Fan, X. et al. Aggregation-induced emission (AIE) nanoparticles-assisted NIR-II fluorescence imaging-guided diagnosis and surgery for inflammatory bowel disease (IBD). Adv. Healthc. Mater. 10, 2101043 (2021).

    Article  CAS  Google Scholar 

  109. Antaris, A. L. et al. A high quantum yield molecule-protein complex fluorophore for near-infrared II imaging. Nat. Commun. 8, 15269 (2017).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  110. Wu, Y. et al. First clinical applications for the NIR-II imaging with ICG in microsurgery. Front. Bioeng. Biotechnol. 10, 1042546 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  111. Carr, J. A., Valdez, T. A., Bruns, O. T. & Bawendi, M. G. Using the shortwave infrared to image middle ear pathologies. Proc. Natl Acad. Sci. USA 113, 9989–9994 (2016).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  112. Shi, X. et al. Zn-doping enhances the photoluminescence and stability of PbS quantum dots for in vivo high-resolution imaging in the NIR-II window. Nano Res. 13, 2239–2245 (2020).

    Article  CAS  Google Scholar 

  113. Magdaong, N. C. M., Niedzwiedzki, D. M., Goodson, C. & Blankenship, R. E. Carotenoid-to-bacteriochlorophyll energy transfer in the LH1–RC core complex of a bacteriochlorophyll b containing purple photosynthetic bacterium blastochloris viridis. J. Phys. Chem. B 120, 5159–5171 (2016).

    Article  CAS  PubMed  Google Scholar 

  114. Chang, Z. et al. Near infrared-II fluorescent protein for in-vivo imaging. Preprint at https://www.biorxiv.org/content/10.1101/2022.03.04.482971v1.full (2022).

  115. Ma, Z., Wang, F., Wang, W., Zhong, Y. & Dai, H. Deep learning for in vivo near-infrared imaging. Proc. Natl Acad. Sci. USA 118, e2021446118 (2021).

    Article  CAS  PubMed  Google Scholar 

  116. Tummers, W. S. et al. Regulatory aspects of optical methods and exogenous targets for cancer detection. Cancer Res. 77, 2197–2206 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Scheuer, W., van Dam, G. M., Dobosz, M., Schwaiger, M. & Ntziachristos, V. Drug-based optical agents: infiltrating clinics at lower risk. Sci. Transl. Med. 4, 134ps111 2012).

    Article  Google Scholar 

  118. DSouza, A., Lin, H., Henderson, E., Samkoe, K. & Pogue, B. Review of fluorescence guided surgery systems: identification of key performance capabilities beyond indocyanine green imaging. J. Biomed. Opt. 21, 080901 (2016).

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  119. Wang, M. et al. Comparing the effective attenuation lengths for long wavelength in vivo imaging of the mouse brain. Biomed. Opt. Express 9, 3534–3543 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

H. Dai acknowledges the National Institutes of Health (NIH DP1-NS-105737) as the sole funding source for the Dai group’s work reviewed in this paper.

Author information

Authors and Affiliations

  1. Department of Electrical and Electronic Engineering, The University of Hong Kong, Hong Kong, China

    Feifei Wang

  2. CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Chinese Academy of Sciences, Beijing, China

    Yeteng Zhong

  3. Department for Functional Imaging in Surgical Oncology, National Center for Tumor Diseases (NCT/UCC) Dresden, Dresden, Germany

    Oliver Bruns

  4. Helmholtz Pioneer Campus, Helmholtz Zentrum München, Neuherberg, Germany

    Oliver Bruns

  5. Department of Materials Science and Engineering, South University of Science and Technology of China, Shenzhen, China

    Yongye Liang

  6. Department of Chemistry and Bio-X, Stanford University, Stanford, CA, USA

    Hongjie Dai

  7. Department of Chemistry, Department of Mechanical Engineering and School of Biomedical Sciences, The University of Hong Kong, Hong Kong, China

    Hongjie Dai

Authors
  1. Feifei Wang
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  2. Yeteng Zhong
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  3. Oliver Bruns
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  4. Yongye Liang
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  5. Hongjie Dai
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Corresponding author

Correspondence to Hongjie Dai.

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Nature Photonics thanks Jun Qian and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Wang, F., Zhong, Y., Bruns, O. et al. In vivo NIR-II fluorescence imaging for biology and medicine. Nat. Photon. (2024). https://doi.org/10.1038/s41566-024-01391-5

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