Skip to main content

Advertisement

SpringerLink
Log in

Recent Advances of Organic Near-Infrared II Fluorophores in Optical Properties and Imaging Functions

  • Review Article
  • Published:
Molecular Imaging and Biology Aims and scope Submit manuscript

Abstract

Near-infrared (NIR) fluorescence imaging (FI) has become a research hotspot because of its distinctive imaging properties: high temporal resolution and sensitivity. Especially in recent years, with the research focus of NIR FI shifting to the NIR-II region, which has better imaging performance, it is expected that NIR FI will find significant applications in the field of in vivo imaging. One of the most crucial directions for research into NIR-II FI is the promotion of novel NIR-II fluorophores with superior imaging properties. The remarkable advantages of organic NIR-II fluorophores in biosafety make them more promising than other fluorescent materials in certain applications. But serious defects in their fluorescence performance preclude particular imaging effects and limit imaging functions. In this review, we summarize and discuss the recent leading literature on overcoming the defects of organic NIR-II fluorophores, demonstrating the potential for further improving their imaging properties. In addition, we cover the functions of NIR-II FI that are promoted by the development of fluorophores, notably including its outlook on molecular imaging in vivo.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.

Similar content being viewed by others

References

  1. Kim RJ, Wu E, Rafael A, Chen EL, Parker MA, Simonetti O, Klocke FJ, Bonow RO, Judd RM (2000) The use of contrast-enhanced magnetic resonance imaging to identify reversible myocardial dysfunction. N Engl J Med 343:1445–1453

    Article  CAS  PubMed  Google Scholar 

  2. Cherry SR et al (2017) Total-body PET: maximizing sensitivity to create new opportunities for clinical research and patient care. J Nucl Med 3

  3. James AP, Dasarathy BV (2014) Medical image fusion: a survey of the state of the art. Inf Fusion 19:4–19

    Article  Google Scholar 

  4. Imbriaco M, Balthazar EJ (2001) Toxic megacolon: role of CT in evaluation and detection of complications. Clin Imaging 25:349–354

    Article  CAS  PubMed  Google Scholar 

  5. Bernd JP et al (2010) PET/MRI: paving the way for the next generation of clinical multimodality imaging applications. J Nucl Med 51

  6. Christoph et al (2008) Dynamic changes in murine vessel geometry assessed by high-resolution magnetic resonance angiography: a 9.4T study.

  7. Li H, Li J (2019) Application of real time contrast-enhanced ultrasound in differential diagnosis of liver malignancies. Can J Physiol Pharmacol 97:341–344

    Article  CAS  PubMed  Google Scholar 

  8. Kang Y, Lee J, Kwon K, Choi C (2010) Dynamic fluorescence imaging of indocyanine green for reliable and sensitive diagnosis of peripheral vascular insufficiency. Microvasc Res 80:552–555

    Article  PubMed  Google Scholar 

  9. Quin G, Liew G, Ho IV, Gillies M, Fraser-Bell S (2013) Diagnosis and interventions for central serous chorioretinopathy: review and update. Clin Exp Ophthalmol 41:187–200

    Article  PubMed  Google Scholar 

  10. Hu Z, Fang C, Li B, Zhang Z, Cao C, Cai M, Su S, Sun X, Shi X, Li C, Zhou T, Zhang Y, Chi C, He P, Xia X, Chen Y, Gambhir SS, Cheng Z, Tian J (2020) 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

    Article  PubMed  Google Scholar 

  11. Chitgupi U, Nyayapathi N, Kim J, Wang D, Sun B, Li C, Carter K, Huang WC, Kim C, Xia J, Lovell JF (2019) Surfactant-stripped micelles for NIR-II photoacoustic imaging through 12 cm of breast tissue and whole human breasts. Adv Mater 31:1902279

    Article  CAS  Google Scholar 

  12. Demos SG et al (2000) Deep subsurface imaging in tissues using spectral and polarization filtering. Opt Express 7:23–28

    Article  CAS  PubMed  Google Scholar 

  13. Zhuoran M et al (2018) Near-infrared IIb fluorescence imaging of vascular regeneration with dynamic tissue perfusion measurement and high spatial resolution. Adv Funct Mater

  14. Hong G, Diao S, Chang J, Antaris AL, Chen C, Zhang B, Zhao S, Atochin DN, Huang PL, Andreasson KI, Kuo CJ, Dai H (2014) Through-skull fluorescence imaging of the brain in a new near-infrared window. Nat Photonics 8:723–730

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Carr JA, Franke D, Caram JR, Perkinson CF, Saif M, Askoxylakis V, Datta M, Fukumura D, Jain RK, Bawendi MG, Bruns OT (2018) Shortwave infrared fluorescence imaging with the clinically approved near-infrared dye indocyanine green. Proc Natl Acad Sci U S A 115:4465–4470

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

  18. Hazra C, Ullah S, Serge Correales YE, Caetano LG, Ribeiro SJL (2018) Enhanced NIR-I emission from water-dispersible NIR-II dye-sensitized core/active shell upconverting nanoparticles. J Mater Chem C 6:4777–4785

    Article  CAS  Google Scholar 

  19. Zhu Y, Gu C, Miao Y, Yu B, Shen Y, Cong H (2019) D-A polymers for fluorescence/photoacoustic imaging and characterization of their photothermal properties. J Mater Chem B 7:6576–6584

    Article  CAS  PubMed  Google Scholar 

  20. Ballou B, Ernst L, Waggoner A (2005) Fluorescence imaging of tumors in vivo. Curr Med Chem 12:795–805

    Article  CAS  PubMed  Google Scholar 

  21. Alford R et al (2009) Toxicity of organic fluorophores used in molecular imaging: literature review. Mol Imaging 8:341

    Article  CAS  PubMed  Google Scholar 

  22. Yu X, Feng Z, Cai Z, Jiang M, Xue D, Zhu L, Zhang Y, Liu J, Que B, Yang W, Xi W, Zhang D, Qian J, Li G (2019) Deciphering of cerebrovasculatures via ICG-assisted NIR-II fluorescence microscopy. J Mater Chem B 7:6623–6629

    Article  CAS  PubMed  Google Scholar 

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

    Book  Google Scholar 

  24. Lever ABP (2009) A career in phthalocyanine chemistry – the Linstead Award 2002. J Porphyrins Phthalocyanines 08:1327–1342

    Article  Google Scholar 

  25. Srikun D, Miller EW, Domaille DW, Chang CJ (2008) An ICT-based approach to ratiometric fluorescence imaging of hydrogen peroxide produced in living cells. J Am Chem Soc 130:4596–4597

    Article  CAS  PubMed  Google Scholar 

  26. Wu Y, Zhu W (2013) Organic sensitizers from D–π–A to D–A–π–A: effect of the internal electron-withdrawing units on molecular absorption, energy levels and photovoltaic performances. Chem Soc Rev 42:2039–2058

    Article  PubMed  Google Scholar 

  27. Li B, Lu L, Zhao M, Lei Z, Zhang F (2018) An efficient 1064 nm NIR-II excitation fluorescent molecular dye for deep-tissue high-resolution dynamic bioimaging. Angew Chem Int Ed 57:7483–7487

    Article  CAS  Google Scholar 

  28. Chen X, Peng X, Cui A, Wang B, Wang L, Zhang R (2006) Photostabilities of novel heptamethine 3H-indolenine cyanine dyes with different N-substituents. J Photochem Photobiol A Chem 181:79–85

    Article  CAS  Google Scholar 

  29. Welch GC et al (2009) Band gap control in conjugated oligomers via Lewis acids. J Am Chem Soc 131:10802

    Article  CAS  PubMed  Google Scholar 

  30. Brymora K, Ducasse L, Delaure A, Hirsch L, Jarrosson T, Niebel C, Serein-Spirau F, Peresutti R, Dautel O, Castet F (2018) Computational design of quadrupolar donor-acceptor-donor molecules with near-infrared light-harvesting capabilities. Dyes Pigments 149:882–892

    Article  CAS  Google Scholar 

  31. Qian G, Wang ZY (2010) Design, synthesis, and properties of benzobisthiadiazole-based donor-pi-acceptor-pi-donor type of low-band-gap chromophores and polymers. Can J Chem 88:192–201

    Article  CAS  Google Scholar 

  32. Qian G, Dai B, Luo M, Yu D, Zhan J, Zhang Z, Ma D, Wang ZY (2008) Band gap tunable, donor-acceptor-donor charge-transfer heteroquinoid-based chromophores: near infrared photoluminescence and electroluminescence. Chem Mater 20:6208–6216

    Article  CAS  Google Scholar 

  33. Mullekom HAMV et al (2001) Developments in the chemistry and band gap engineering of donor–acceptor substituted conjugated polymers. Mater Sci Eng R Rep 32:1–40

    Article  Google Scholar 

  34. Zhou Y, Wang D, Zhang Y, Chitgupi U, Geng J, Wang Y, Zhang Y, Cook TR, Xia J, Lovell JF (2016) A phosphorus phthalocyanine formulation with intense absorbance at 1000 nm for deep optical imaging. Theranostics 6:688–697

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Bai L, Sun P, Liu Y, Zhang H, Hu W, Zhang W, Liu Z, Fan Q, Li L, Huang W (2019) Novel aza-BODIPY based small molecular NIR-II fluorophores for in vivo imaging. Chem Commun 55:10920–10923

    Article  CAS  Google Scholar 

  36. Zhang M et al (2018) Bright quantum dots emitting at ∼1,600 nm in the NIR-IIb window for deep tissue fluorescence imaging. Chem Sci 115:201806153

    Google Scholar 

  37. Mishra A, Behera RK, Behera PK, Mishra BK, Behera GB (2000) Cyanines during the 1990s: a review. Chem Rev 100:1973–2012

    Article  CAS  PubMed  Google Scholar 

  38. Sun Y, Qu C, Chen H, He M, Tang C, Shou K, Hong S, Yang M, Jiang Y, Ding B, Xiao Y, Xing L, Hong X, Cheng Z (2016) Novel benzo-bis(1,2,5-thiadiazole) fluorophores for in vivo NIR-II imaging of cancer. Chem Sci 7:6203–6207

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Konishi et al (2016) Recent advances in twisted intramolecular charge transfer (TICT) fluorescence and related phenomena in materials chemistry

  40. Hong Y et al (2009) Aggregation-induced emission: phenomenon, mechanism and applications. Chem Commun 4332

  41. Wu W et al (2019) Molecular engineering of an organic NIR-II fluorophore with aggregation-induced emission characteristics for in vivo imaging. Small:15

  42. Wu W, Yang YQ, Yang Y, Yang YM, Wang H, Zhang KY, Guo L, Ge HF, Liu J, Feng H (2019) An organic NIR-II nanofluorophore with aggregation-induced emission characteristics for in vivo fluorescence imaging. Int J Nanomedicine 14:3571–3582

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Zhang R, Duan Y, Liu B (2019) Recent advances of AIE dots in NIR imaging and phototherapy. Nanoscale 11:19241–19250

    Article  CAS  PubMed  Google Scholar 

  44. Lin J, Zeng X, Xiao Y, Tang L, Nong J, Liu Y, Zhou H, Ding B, Xu F, Tong H, Deng Z, Hong X (2019) Novel near-infrared II aggregation-induced emission dots for in vivo bioimaging. Chem Sci 10:1219–1226

    Article  CAS  PubMed  Google Scholar 

  45. Zhang X et al (2016) Traumatic brain injury imaging in the second near-infrared window with a molecular fluorophore. Adv Mater 28:6872

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

  47. Yang Q, Hu Z, Zhu S, Ma R, Ma H, Ma Z, Wan H, Zhu T, Jiang Z, Liu W, Jiao L, Sun H, Liang Y, Dai H (2018) Donor engineering for NIR-II molecular fluorophores with enhanced fluorescent performance. J Am Chem Soc 140:1715–1724

    Article  CAS  PubMed  Google Scholar 

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

  49. Gao S et al (2019) Albumin tailoring fluorescence and photothermal conversion effect of near-infrared-II fluorophore with aggregation-induced emission characteristics. Nat Commun:10

  50. Liu S, Zhou X, Zhang H, Ou H, Lam JWY, Liu Y, Shi L, Ding D, Tang BZ (2019) Molecular motion in aggregates: manipulating TICT for boosting photothermal theranostics. J Am Chem Soc 141:5359–5368

    Article  CAS  PubMed  Google Scholar 

  51. Wang Q, Xia B, Xu J, Niu X, Cai J, Shen Q, Wang W, Huang W, Fan Q (2019) Biocompatible small organic molecule phototheranostics for NIR-II fluorescence/photoacoustic imaging and simultaneous photodynamic/photothermal combination therapy. Mater Chem Front 3:650–655

    Article  CAS  Google Scholar 

  52. Xu L et al (2019) Indocyanine green and poly I:C containing thermo-responsive liposomes used in immune-photothermal therapy prevent cancer growth and metastasis. J Immunother Cancer:7

  53. Yang X et al (2019) Indocyanine green (ICG) - menthol loaded cerasomal nanoparticles for ultrasound imaging and photothermal therapy against tumor. Mater Lett 255

  54. Zhang R, Wang Z, Xu L, Xu Y, Lin Y, Zhang Y, Sun Y, Yang G (2019) Rational design of a multifunctional molecular dye with single dose and laser for efficiency NIR-II fluorescence/photoacoustic imaging guided photothermal therapy. Anal Chem 91:12476–12483

    Article  CAS  PubMed  Google Scholar 

  55. Hong G et al (2012) Multifunctional in vivo vascular imaging using near-infrared II fluorescence. Nat Med 18:1841

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Antaris AL et al (2016) A small-molecule dye for NIR-II imaging. Nat Mater 15:235

    Article  CAS  PubMed  Google Scholar 

  57. Shou K et al (2017) Multifunctional biomedical imaging in physiological and pathological conditions using a NIR-II probe. Adv Funct Mater:27

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Ding F, Zhan Y, Lu X, Sun Y (2018) Recent advances in near-infrared II fluorophores for multifunctional biomedical imaging. Chem Sci 9:4370–4380

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Antaris AL et al (2017) A high quantum yield molecule-protein complex fluorophore for near-infrared II imaging. Nat Commun:8

  61. Li D et al (2019) Monitoring the real-time circulatory system-related physiological and pathological processes in vivo using a multifunctional NIR-II probe. Adv Funct Mater

  62. Ye Z, Yang W, Wang C, Zheng Y, Chi W, Liu X, Huang Z, Li X, Xiao Y (2019) Quaternary piperazine-substituted rhodamines with enhanced brightness for super-resolution imaging. J Am Chem Soc 141:14491–14495

    Article  CAS  PubMed  Google Scholar 

  63. Louie A (2010) Multimodality imaging probes: design and challenges. 110 3146-95

  64. Zhou H et al (2019) Specific small-molecule NIR-II fluorescence imaging of osteosarcoma and lung metastasis. Adv Healthc Mater

    Google Scholar 

  65. Feng W, Zhang Y, Li Z, Zhai S, Lv W, Liu Z (2019) Lighting up NIR-II fluorescence in vivo: an activable probe for noninvasive hydroxyl radical imaging. Anal Chem 91:15757–15762

    Article  CAS  PubMed  Google Scholar 

  66. Tang Y et al (2019) Bio-erasable intermolecular donor-acceptor interaction of organic semiconducting nanoprobes for activatable NIR-II fluorescence imaging. Adv Funct Mater:29

  67. Zhang N et al (2019) An efficient fluorescence sensor for nitroreductase selective imaging based on intramolecular photoinduced electron transfer. Talanta:205

  68. Zhang W et al (2019) Rational design of stable near-infrared cyanine-based probe with remarkable large Stokes shift for monitoring carbon monoxide in living cells and in vivo. Dyes Pigments:171

  69. Bokan M, Gellerman G, Patsenker LD (2019) Drug delivery platform comprising long-wavelength fluorogenic phenolo-cyanine dye for real-time monitoring of drug release. Dyes Pigments 171:107703

    Article  CAS  Google Scholar 

  70. Mu X et al (2019) A cyanine-derived near-infrared molecular rotor for ratiometric imaging of mitochondrial viscosity in cells. Sensors Actuators B Chem:298

  71. Li H, Shi W, Li X, Hu Y, Fang Y, Ma H (2019) Ferroptosis accompanied by (OH)-O-center dot generation and cytoplasmic viscosity increase revealed via dual-functional fluorescence probe. J Am Chem Soc 141:18301–18307

    Article  CAS  PubMed  Google Scholar 

  72. Tang Y et al (2018) “Dual lock-and-key”-controlled nanoprobes for ultrahigh specific fluorescence imaging in the second near-infrared window. Adv Mater 30

  73. Zhu S et al (2018) Repurposing cyanine NIR-I dyes accelerates clinical translation of near-infrared-II (NIR-II) bioimaging. Adv Mater 30

  74. Chen Q, Chen J, He M, Bai Y, Yan H, Zeng N, Liu F, Wen S, Song L, Sheng Z, Liu C, Fang C (2019) Novel small molecular dye-loaded lipid nanoparticles with efficient near-infrared-II absorption for photoacoustic imaging and photothermal therapy of hepatocellular carcinoma. Biomater Sci 7:3165–3177

    Article  CAS  PubMed  Google Scholar 

  75. Zhang Q et al (2019) Hierarchically nanostructured hybrid platform for tumor delineation and image-guided surgery via NIR-II fluorescence and PET bimodal imaging. Small:15

  76. Yoon H et al (2017) Liposomal indocyanine green for enhanced photothermal therapy. ACS Appl Mater Interfaces 9:5683–5691

    Article  CAS  PubMed  Google Scholar 

  77. Miranda D, Wan C, Kilian HI, Mabrouk MT, Zhou Y, Jin H, Lovell JF (2019) Indocyanine green binds to DOTAP liposomes for enhanced optical properties and tumor photoablation. Biomater Sci 7:3158–3164

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Sun C, Li B, Zhao M, Wang S, Lei Z, Lu L, Zhang H, Feng L, Dou C, Yin D, Xu H, Cheng Y, Zhang F (2019) J-Aggregates of cyanine dye for NIR-II in vivo dynamic vascular imaging beyond 1500 nm. J Am Chem Soc 141:19221–19225

    Article  CAS  PubMed  Google Scholar 

  79. Zian W et al (2020) Small molecular interaction-based fluorescence enhancement for second near-infrared imaging. Nanomedicine 0

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

    Article  CAS  Google Scholar 

  81. Chen L et al (2020) Diagnostic efficacy and molecular testing by combined fine needle aspiration and core needle biopsy in patients with a lung nodule. Cancer Cytopathol

    Book  Google Scholar 

  82. Fu Y, Zhang YY, Cui LG, Tan S, Sun Y (2019) Ultrasound-guided biopsy of pleural-based pulmonary lesions by injection of contrast-enhancing drugs. Front Pharmacol 10:960

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This review was supported by the National Natural Science Foundation of China (grant number 81671745) and Suzhou key industry technology innovation project (grant number SYG201912).

Author information

Authors and Affiliations

  1. State Key Laboratory of Bioelectronics, Jiangsu Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China

    Haoli Yu & Min Ji

Authors
  1. Haoli Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Min Ji
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Min Ji.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yu, H., Ji, M. Recent Advances of Organic Near-Infrared II Fluorophores in Optical Properties and Imaging Functions. Mol Imaging Biol 23, 160–172 (2021). https://doi.org/10.1007/s11307-020-01545-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11307-020-01545-1

Key words

Search

Navigation