Skip to main content

Advertisement

SpringerLink
Log in

Recent advances in aggregation-induced emission luminogens in photoacoustic imaging

  • Review Article
  • Published:
European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Photoacoustic imaging (PAI) is a rapidly emerging modality in biomedical research with the advantages of noncontact operation, high optical resolution, and deep penetration. Great efforts and progress in the development of PAI agents with improved imaging resolution and sensitivity have been made over the past 2 decades. Among them, organic agents are the most promising candidates for preclinical/clinical applications due to their outstanding in vivo properties and facile biofunctionalities. Motivated by the unique properties of aggregation-induced emission (AIE) luminogens (AIEgens), various optical probes have been developed for bioanalyte detection, multimodal bioimaging, photodynamic/photothermal therapy, and imaging-guided therapeutics. In particular, AIE-active contrast agents have been demonstrated in PAI applications with excellent performance in imaging resolution and tissue permeability in vivo. This paper presents a brief overview of recent progress in AIE-based agents in the field of photoacoustic imaging. In particular, we focus on the basic concepts, data sorting and comparison, developing trends, and perspectives of photoacoustic imaging. Through numerous typical examples, the way each system realizes the desired photoacoustic performance in various biomedical applications is clearly illustrated. We believe that AIE-based PAI agents would be promising multifunctional theranostic platforms in clinical fields and will facilitate significant advancements in this research topic.

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
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Scheme 1

Similar content being viewed by others

References

  1. Sun Y, Jiang H, O’Neill BE. Photoacoustic imaging: an emerging optical modality in diagnostic and theranostic medicine. J Biosens Bioelectron. 2011;2:3. https://doi.org/10.4172/2155-6210.1000108.

    Article  Google Scholar 

  2. Bell AG. On the production and reproduction of sound by light. American Journal of Science. 1880;s3-20(118):305.

    Article  Google Scholar 

  3. Hosseinaee Z, Le M, Bell K, Reza PH. Towards non-contact photoacoustic imaging [review]. Photoacoustics. 2020;20:100207.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Beard P. Biomedical photoacoustic imaging. Interface Focus. 2011;1(4):602–31.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Karthikesh MS, Yang X. Photoacoustic image-guided interventions. Exp Biol Med. 2019;245(4):153537021988932.

    Google Scholar 

  6. Furdella KJ, Witte RS, Vande Geest JP. Tracking delivery of a drug surrogate in the porcine heart using photoacoustic imaging and spectroscopy. J Biomed Opt. 2017;22(4):41016.

    Article  PubMed  Google Scholar 

  7. Wang J, Chen F, Arconada-Alvarez SJ, Hartanto J, Yap LP, Park R, Wang F, Vorobyova I, Dagliyan G, Conti PS, et al. A nanoscale tool for photoacoustic-based measurements of clotting time and therapeutic drug monitoring of heparin. Nano Lett. 2016;16(10):6265–71.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Duan Z, Gao YJ, Qiao ZY, Fan G, Liu Y, Zhang D, Wang H. A photoacoustic approach for monitoring the drug release of pH-sensitive poly(β-amino ester)s. J Mater Chem B. 2014;2(37):6271–82.

    Article  PubMed  CAS  Google Scholar 

  9. Cash KJ, Li C, Xia J, Wang LV, Clark HA. Optical drug monitoring: photoacoustic imaging of nanosensors to monitor therapeutic lithium in vivo. ACS Nano. 2015;9(2):1692–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Jung HS, Verwilst P, Sharma A, Shin J, Sessler JL, Kim JS. Organic molecule-based photothermal agents: an expanding photothermal therapy universe. Chem Soc Rev. 2018;47(7):2280–97.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Lediju Bell MA, Ostrowski AK, Li K, Kazanzides P, Boctor EM. Localization of transcranial targets for photoacoustic-guided endonasal surgeries. Photoacoustics. 2015;3(2):78–87.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Matthews TP, Zhang C, Yao DK, Maslov K, Wang LV. Label-free photoacoustic microscopy of peripheral nerves. J Biomed Opt. 2014;19(1):16004.

    Article  PubMed  Google Scholar 

  13. Shubert J, Lediju Bell MA. Photoacoustic imaging of a human vertebra: implications for guiding spinal fusion surgeries. Phys Med Biol. 2018;63(14):144001.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Lediju Bell MA, Shubert J. Photoacoustic-based visual servoing of a needle tip. Sci Rep. 2018;8(1):15519.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Wang H, Liu S, Wang T, Zhang C, Feng T, Tian C. Three-dimensional interventional photoacoustic imaging for biopsy needle guidance with a linear array transducer. J Biophotonics. 2019;12(12):e201900212.

    Article  PubMed  CAS  Google Scholar 

  16. Witte RS, Karunakaran C, Zuniga AN, Schmitz H, Arif H. Frontiers of cancer imaging and guided therapy using ultrasound, light, and microwaves. Clin Exp Metastasis. 2018;35(5–6):413–8.

    Article  PubMed  CAS  Google Scholar 

  17. Pan D, Kim B, Wang LV, Lanza GM. A brief account of nanoparticle contrast agents for photoacoustic imaging. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2013;5(6):517–43.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Weber J, Beard PC, Bohndiek SE. Contrast agents for molecular photoacoustic imaging. Nat Methods. 2016;13(8):639–50.

    Article  PubMed  CAS  Google Scholar 

  19. Nie L, Chen X. Structural and functional photoacoustic molecular tomography aided by emerging contrast agents. Chem Soc Rev. 2014;43(20):7132–70.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Fan Q, Cheng K, Hu X, Ma X, Zhang R, Yang M, Lu X, Xing L, Huang W, Gambhir SS, et al. Transferring biomarker into molecular probe: melanin nanoparticle as a naturally active platform for multimodality imaging. J Am Chem Soc. 2014;136(43):15185–94.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Sangha GS, Phillips EH, Goergen CJ. In vivo photoacoustic lipid imaging in mice using the second near-infrared window. Biomed Opt Express. 2017;8(2):736–42.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Wang P, Wang P, Wang HW, Cheng JX. Mapping lipid and collagen by multispectral photoacoustic imaging of chemical bond vibration. J Biomed Opt. 2012;17(9):96010–1.

    Article  PubMed  Google Scholar 

  23. Stoffels I, Morscher S, Helfrich I, Hillen U, Leyh J, Burton NC, Sardella TC, Claussen J, Poeppel TD, Bachmann HS, et al. Metastatic status of sentinel lymph nodes in melanoma determined noninvasively with multispectral optoacoustic imaging. Sci Transl Med. 2015;7(317):317ra199.

    Article  PubMed  CAS  Google Scholar 

  24. Ho CJ, Balasundaram G, Driessen W, McLaren R, Wong CL, Dinish US, Attia AB, Ntziachristos V, Olivo M. Multifunctional photosensitizer-based contrast agents for photoacoustic imaging. Sci Rep. 2014;4:5342.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Wang LV, Yao J. A practical guide to photoacoustic tomography in the life sciences. Nat Methods. 2016;13(8):627–38.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Li JC, Pu KY. Development of organic semiconducting materials for deep-tissue optical imaging, phototherapy and photoactivation. Chem Soc Rev. 2019;48(1):38–71.

    Article  PubMed  CAS  Google Scholar 

  27. Fu QR, Zhu R, Song JB, Yang HH, Chen XY. Photoacoustic imaging: contrast agents and their biomedical applications. Adv Mater. 2019;31(6):e1805875. https://doi.org/10.1002/adma.201805875.

  28. Li W, Chen X. Gold nanoparticles for photoacoustic imaging. Nanomedicine (Lond). 2015;10(2):299–320.

    Article  CAS  Google Scholar 

  29. Lin J, Chen X, Huang P. Graphene-based nanomaterials for bioimaging. Adv Drug Deliv Rev. 2016;105(Pt B):242–54.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Chen Y, Tan C, Zhang H, Wang L. Two-dimensional graphene analogues for biomedical applications. Chem Soc Rev. 2015;44(9):2681–701.

    Article  PubMed  CAS  Google Scholar 

  31. Li J, Rao J, Pu K. Recent progress on semiconducting polymer nanoparticles for molecular imaging and cancer phototherapy. Biomaterials. 2018;155:217–35.

    Article  PubMed  CAS  Google Scholar 

  32. Moon GD, Choi SW, Cai X, Li W, Cho EC, Jeong U, Wang LV, Xia Y. A new theranostic system based on gold nanocages and phase-change materials with unique features for photoacoustic imaging and controlled release. J Am Chem Soc. 2011;133(13):4762–5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Filonov GS, Krumholz A, Xia J, Yao J, Wang LV, Verkhusha VV. Deep-tissue photoacoustic tomography of a genetically encoded near-infrared fluorescent probe. Angew Chem Int Ed Engl. 2012;51(6):1448–51.

    Article  PubMed  CAS  Google Scholar 

  34. Wang X, Ku G, Wegiel MA, Bornhop DJ, Stoica G, Wang LV. Noninvasive photoacoustic angiography of animal brains in vivo with near-infrared light and an optical contrast agent. Opt Lett. 2004;29(7):730–2.

    Article  PubMed  Google Scholar 

  35. Ou H, Li J, Chen C, Gao H, Xue X, Ding D. Organic/polymer photothermal nanoagents for photoacoustic imaging and photothermal therapy in vivo. Sci China Mater. 2019;62(11):1740–58.

    Article  CAS  Google Scholar 

  36. Luu T, Li W, O’Brien-Simpson NM, Hong Y. Recent applications of aggregation induced emission probes for antimicrobial peptide studies. Chemistry An Asian Journal. 2021;16(9):1027–40.

    Article  PubMed  CAS  Google Scholar 

  37. Alam P, Leung NLC, Zhang J, Kwok RTK, Lam JWY, Tang BZ. AIE-based luminescence probes for metal ion detection. Coord Chem Rev. 2021;429:213693.

    Article  CAS  Google Scholar 

  38. Wu WB, Li Z. Nanoprobes with aggregation-induced emission for theranostics. Materials Chemistry Frontiers. 2021;5(2):603–26.

    Article  CAS  Google Scholar 

  39. Feng GX, Liu B. Multifunctional AIEgens for future theranostics. Small. 2016;12(47):6528–35.

    Article  PubMed  CAS  Google Scholar 

  40. Liu Y, Bhattarai P, Dai Z, Chen X. Photothermal therapy and photoacoustic imaging via nanotheranostics in fighting cancer. Chem Soc Rev. 2019;48(7):2053–108.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Ong SY, Zhang CY, Dong X, Yao SQ. Recent advances in polymeric nanoparticles for enhanced fluorescence and photoacoustic imaging. Angewandte Chemie-International Edition. 2021;60(33):17797–809.

    Article  PubMed  CAS  Google Scholar 

  42. Li C, Liu C, Fan Y, Ma X, Zhan Y, Lu X, Sun Y. Recent development of near-infrared photoacoustic probes based on small-molecule organic dye. RSC Chem Biol. 2021;2(3):743–58.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Li K, Liu B. Polymer-encapsulated organic nanoparticles for fluorescence and photoacoustic imaging. Chem Soc Rev. 2014;43(18):6570–97.

    Article  PubMed  CAS  Google Scholar 

  44. He Z, Ke C, Tang BZ. Journey of aggregation-induced emission research. ACS Omega. 2018;3(3):3267–77.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Ma X, Sun R, Cheng J, Liu J, Gou F, Xiang H, Zhou X. Fluorescence aggregation-caused quenching versus aggregation-induced emission: a visual teaching technology for undergraduate chemistry students. J Chem Educ. 2016;93(2):345–50.

    Article  CAS  Google Scholar 

  46. Yang J-S, Swager TM. Fluorescent porous polymer films as TNT chemosensors: electronic and structural effects. J Am Chem Soc. 1998;120(46):11864.

    Article  CAS  Google Scholar 

  47. Luo J, Xie Z, Lam JW, Cheng L, Chen H, Qiu C, Kwok HS, Zhan X, Liu Y, Zhu D, et al. Aggregation-induced emission of 1-methyl-1,2,3,4,5-pentaphenylsilole. Chem Commun (Camb). 2001;18:1740–1.

    Article  Google Scholar 

  48. Leung NLC, Xie N, Yuan W, Liu Y, Wu Q, Peng Q, Miao Q, Lam JWY, Tang BZ. Restriction of intramolecular motions: the general mechanism behind aggregation-induced emission. Chemistry A European Journal. 2014;20(47):15349–53.

    Article  PubMed  CAS  Google Scholar 

  49. Chen Y, Lam JWY, Kwok RTK, Liu B, Tang BZ. Aggregation-induced emission: fundamental understanding and future developments. Mater Horiz. 2019;6(3):428–33.

    Article  CAS  Google Scholar 

  50. Zhang JY, Zhang HK, Lam JWY, Tang BZ. Restriction of intramolecular motion(RIM): investigating AIE mechanism from experimental and theoretical studies. Chem Res Chin Univ. 2021;37(1):1–15.

    Article  CAS  Google Scholar 

  51. Peng Q, Shuai Z. Molecular mechanism of aggregation-induced emission. Aggregate. 2021;2(5):e91.

    Google Scholar 

  52. Upputuri PK, Pramanik M. Photoacoustic imaging in the second near-infrared window: a review. J Biomed Opt. 2019;24(4):1–20.

    Article  PubMed  Google Scholar 

  53. Zhang ZJ, Xu WH, Kang MM, Wen HF, Guo H, Zhang PF, Xi L, Li K, Wang L, Wang D, et al. An all-round athlete on the track of phototheranostics: subtly regulating the balance between radiative and nonradiative decays for multimodal imaging-guided synergistic therapy. Adv Mater. 2020;32(36):e2003210. https://doi.org/10.1002/adma.202003210.

  54. Zhao Z, Chen C, Wu W, Wang F, Du L, Zhang X, Xiong Y, He X, Cai Y, Kwok RTK, et al. Highly efficient photothermal nanoagent achieved by harvesting energy via excited-state intramolecular motion within nanoparticles. Nat Commun. 2019;10(1):768.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Li HX, Wen HF, Li J, Huang JC, Wang D, Tang BZ. Doping AIE photothermal molecule into all-fiber aerogel with self-pumping water function for efficiency solar steam generation. ACS Appl Mater Interfaces. 2020;12(23):26033–40.

    Article  PubMed  CAS  Google Scholar 

  56. Xu Z, Tang BZ, Wang Y, Ma DG. Recent advances in high performance blue organic light-emitting diodes based on fluorescence emitters. Journal of Materials Chemistry C. 2020;8(8):2614–42.

    Article  CAS  Google Scholar 

  57. Gao M, Tang BZ. Fluorescent sensors based on aggregation-induced emission: recent advances and perspectives. Acs Sensors. 2017;2(10):1382–99.

    Article  PubMed  CAS  Google Scholar 

  58. Geng J, Liao L-D, Qin W, Tang BZ, Thakor N, Liu B. Fluorogens with aggregation induced emission: ideal photoacoustic contrast reagents due to intramolecular rotation. J Nanosci Nanotechnol. 2015;15(2):1864–8.

    Article  PubMed  CAS  Google Scholar 

  59. He XW, Peng C, Qiang SJ, Xiong LH, Zhao Z, Wang ZY, Kwok RTK, Lam JWY, Ma N, Tang BZ. Less is more: silver-AIE core@shell nanoparticles for multimodality cancer imaging and synergistic therapy. Biomaterials. 2020;238:119834. https://doi.org/10.1016/j.biomaterials.2020.119834.

    Article  PubMed  CAS  Google Scholar 

  60. Welsher K, Liu Z, Sherlock SP, Robinson JT, Chen Z, Daranciang D, Dai H. A route to brightly fluorescent carbon nanotubes for near-infrared imaging in mice. Nat Nanotechnol. 2009;4(11):773–80.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Zha ML, Lin XW, Ni JS, Li YX, Zhang YC, Zhang X, Wang LD, Li K. An ester-substituted semiconducting polymer with efficient nonradiative decay enhances NIR-II photoacoustic performance for monitoring of tumor growth. Angewandte Chemie-International Edition. 2020;59(51):23268–76.

    Article  PubMed  CAS  Google Scholar 

  62. Wang LV, Hu S. Photoacoustic tomography: in vivo imaging from organelles to organs. Science. 2012;335(6075):1458–62.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Erfanzadeh M, Zhu Q. Photoacoustic imaging with low-cost sources; a review. Photoacoustics. 2019;14:1–11.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Wu J, You L, Lan L, Lee HJ, Chaudhry ST, Li R, Cheng JX, Mei J. Semiconducting polymer nanoparticles for centimeters-deep photoacoustic imaging in the second near-infrared window. Adv Mater. 2017;29(41). https://doi.org/10.1002/adma.201703403.

  65. Jiang Y, Upputuri PK, Xie C, Lyu Y, Zhang L, Xiong Q, Pramanik M, Pu K. Broadband absorbing semiconducting polymer nanoparticles for photoacoustic imaging in second near-infrared window. Nano Lett. 2017;17(8):4964–9.

    Article  PubMed  CAS  Google Scholar 

  66. Du WT, Liu XL, Liu LJ, Lam JWY, Tang BZ. Photoresponsive polymers with aggregation-induced emission. Acs Applied Polymer Materials. 2021;3(5):2290–309.

    Article  CAS  Google Scholar 

  67. Wang Z, Zhou Y, Xu R, Xu Y, Dang D, Shen Q, Meng L, Tang BZ. Seeing the unseen: AIE luminogens for super-resolution imaging. Coordination Chemistry Reviews. 2022;451:214279.

    Article  CAS  Google Scholar 

  68. Kim D, Kim J, Park YI, Lee N, Hyeon T. Recent development of inorganic nanoparticles for biomedical imaging. ACS Cent Sci. 2018;4(3):324–36.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  69. Chen Y-S, Zhao Y, Beinat C, Zlitni A, Hsu E-C, Chen D-H, Achterberg F, Wang H, Stoyanova T, Dionne J, et al. Ultra-high-frequency radio-frequency acoustic molecular imaging with saline nanodroplets in living subjects. Nat Nanotechnol. 2021;16(6):717–24.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. Attia ABE, Balasundaram G, Moothanchery M, Dinish US, Bi R, Ntziachristos V, Olivo M. A review of clinical photoacoustic imaging: current and future trends. Photoacoustics. 2019;16:100144.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Wang Z, Kumar UP, Zhen X, Zhang R, Jiang Y, Ai X, Zhang Z, Ming H, Meng Z, Lu Y. pH-sensitive and biodegradable charge-transfer nanocomplex for second near-infrared photoacoustic tumor imaging. Nano Res. 2019:1–7. https://doi.org/10.1007/s12274-018-2175-9.

  72. Liu SJ, Li YY, Kwok RTK, Lam JWY, Tang BZ. Structural and process controls of AIEgens for NIR-II theranostics. Chem Sci. 2021;12(10):3427–36.

    Article  CAS  Google Scholar 

  73. Xu YZ, Li CB, Xu RH, Zhang N, Wang Z, Jing XN, Yang ZW, Dang DF, Zhang PF, Meng LJ. Tuning molecular aggregation to achieve highly bright AIE dots for NIR-II fluorescence imaging and NIR-I photoacoustic imaging. Chem Sci. 2020;11(31):8157–66.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Xu YZ, Dang DF, Zhu HR, Jing XA, Zhu X, Zhang N, Li CB, Zhao YZ, Zhang PF, Yang ZW, et al. Boosting the AIEgen-based photo-theranostic platform by balancing radiative decay and non-radiative decay. Materials Chemistry Frontiers. 2021;5(11):4182–92.

    Article  CAS  Google Scholar 

  75. Soto AM, Longo G, Montévil M, Sonnenschein C. The biological default state of cell proliferation with variation and motility, a fundamental principle for a theory of organisms. Prog Biophys Mol Biol. 2016;122(1):16–23.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Meir R, Motiei M, Popovtzer R. Gold nanoparticles for in vivo cell tracking. Nanomedicine. 2014;9(13):2059–69.

    Article  PubMed  CAS  Google Scholar 

  77. Xu W, Dong S, Han Y, Li S, Liu Y. Hydrogels as antibacterial biomaterials. Curr Pharm Des. 2018;24(8):843–54.

    Article  PubMed  CAS  Google Scholar 

  78. Zhang M, Wang Z, Huang P, Jiang G, Xu C, Zhang W, Guo R, Li W, Zhang X. Real-time and noninvasive tracking of injectable hydrogel degradation using functionalized AIE nanoparticles. Nanophotonics. 2020;9(7):2063–75.

    Article  CAS  Google Scholar 

  79. Langen KJ, Galldiks N, Hattingen E, Shah NJ. Advances in neuro-oncology imaging. Nat Rev Neurol. 2017;13(5):279–89.

    Article  PubMed  Google Scholar 

  80. Yang X, Chen YH, Xia F, Sawan M. Photoacoustic imaging for monitoring of stroke diseases: a review. Photoacoustics. 2021;23:100287.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Sheng Z, Guo B, Hu D, Xu S, Wu W, Liew WH, Yao K, Jiang J, Liu C Zheng H, Liu B. Bright aggregation-induced-emission dots for targeted synergetic NIR-II fluorescence and NIR-I Photoacoustic imaging of orthotopic brain tumors. Adv Mater. 2018:e1800766. https://doi.org/10.1002/adma.201800766.

  82. Zhang Y, Jeon M, Rich LJ, Hong H, Geng J, Zhang Y, Shi S, Barnhart TE, Alexandridis P, Huizinga JD, et al. Non-invasive multimodal functional imaging of the intestine with frozen micellar naphthalocyanines. Nat Nanotechnol. 2014;9(8):631–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  83. Jiang Z, Sun B, Wang Y, Gao H, Ren H, Zhang H, Lu T, Ren X, Wei W, Wang X, Zhang L, Li J, Ding D, Lovell JF, Zhang Y. Surfactant-stripped micelles with aggregation-induced enhanced emission for bimodal gut imaging in vivo and microbiota tagging ex vivo. Adv Healthc Mater. 2021;10(24):e2100356. https://doi.org/10.1002/adhm.202100356.

  84. Hu F, Qi G. Kenry, Mao D, Zhou S, Wu M, Wu W, Liu B: Visualization and insitu ablation of intracellular bacterial pathogens through metabolic labeling. Angew Chem Int Ed. 2020;59(24):9288–92.

    Article  CAS  Google Scholar 

  85. Hu XM, Li ZX, Lin RH, Shan JQ, Yu QW, Wang RX, Liao LS, Yan WT, Wang Z, Shang L, et al. Guidelines for regulated cell death assays: a systematic summary, a categorical comparison, a prospective. Front Cell Dev Biol. 2021;9:634690.

    Article  PubMed  PubMed Central  Google Scholar 

  86. Zhang WW, Ding XY, Cheng H, Yin CY, Yan J, Mou ZP, Wang WY, Cui DX, Fan CD, Sun DD. Dual-targeted gold nanoprism for recognition of early apoptosis, dual-model imaging and precise cancer photothermal therapy. Theranostics. 2019;9(19):5610–25.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  87. Joseph JP, Harishankar MK, Pillai AA, Devi A. Hypoxia induced EMT: a review on the mechanism of tumor progression and metastasis in OSCC. Oral Oncol. 2018;80:23–32.

    Article  PubMed  CAS  Google Scholar 

  88. Lee JW, Ko J, Ju C, Eltzschig HK. Hypoxia signaling in human diseases and therapeutic targets. Exp Mol Med. 2019;51(6):1–13. https://doi.org/10.1038/s12276-019-0235-1.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  89. Boedtkjer E, Pedersen SF. The acidic tumor microenvironment as a driver of cancer. Annu Rev Physiol. 2020;82:103–26. https://doi.org/10.1146/annurev-physiol-021119-034627.

    Article  PubMed  CAS  Google Scholar 

  90. Neri D, Supuran CT. Interfering with pH regulation in tumours as a therapeutic strategy. Nat Rev Drug Discovery. 2011;10(10):767–77.

    Article  PubMed  CAS  Google Scholar 

  91. Tejero J, Shiva S, Gladwin MT. Sources of vascular nitric oxide and reactive oxygen species and their regulation. Physiol Rev. 2019;99(1):311–79.

    Article  PubMed  CAS  Google Scholar 

  92. Weissleder R, Pittet MJ. Imaging in the era of molecular oncology. Nature. 2008;452(7187):580–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  93. Chong WK, Papadopoulou V, Dayton PA. Imaging with ultrasound contrast agents: current status and future. Abdom Radiol (NY). 2018;43(4):762–72.

    Article  Google Scholar 

  94. Kobayashi H, Ogawa M, Alford R, Choyke PL, Urano Y. New strategies for fluorescent probe design in medical diagnostic imaging. Chem Rev. 2010;110(5):2620–40.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  95. Fang HY, Stangl S, Marcazzan S, Carvalho MJB, Baumeister T, Anand A, Strangmann J, Huspenina JS, Wang TC, Schmid RM, Feith M, Friess H, Ntziachristos V, Multhoff G, Gorpas D, Quante M. Targeted Hsp70 fluorescence molecular endoscopy detects dysplasia in Barrett’s esophagus. Eur J Nucl Med Mol Imaging. 2021. https://doi.org/10.1007/s00259-021-05582-y.

  96. Lucero MY, East AK, Reinhardt CJ, Sedgwick AC, Su S, Lee MC, Chan J. Development of NIR-II photoacoustic probes tailored for deep-tissue sensing of nitric oxide. J Am Chem Soc. 2021;143(18):7196–202.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  97. Zhang J, He B, Hu Y, Alam P, Zhang H, Lam JWY, Tang BZ. Stimuli-responsive AIEgens. Adv Mater. 2021;33(32):2008071.

    Article  CAS  Google Scholar 

  98. Liang J, Tang B, Liu B. Specific light-up bioprobes based on AIEgen conjugates. Chem Soc Rev. 2015;44(10):2798–811.

    Article  PubMed  CAS  Google Scholar 

  99. Kobayashi H, Choyke PL. Target-cancer-cell-specific activatable fluorescence imaging probes: rational design and in vivo applications. Acc Chem Res. 2011;44(2):83–90.

    Article  PubMed  CAS  Google Scholar 

  100. Li M, Li H, Wu Q, Niu N, Huang J, Zhang L, Li Y, Wang D, Tang BZ. Hypoxia-activated probe for NIR fluorescence and photoacoustic dual-mode tumor imaging. iScience. 2021;24(3):102261.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  101. Xu L, Sun L, Zeng F, Wu S. Activatable fluorescent probe based on aggregation-induced emission for detecting hypoxia-related pathological conditions. Anal Chim Acta. 2020;1125:152–61.

    Article  PubMed  CAS  Google Scholar 

  102. Vordermark D. Hypoxia-specific targets in cancer therapy: role of splice variants. BMC Med. 2010;8:45.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  103. Wouters BG, Weppler SA, Koritzinsky M, Landuyt W, Nuyts S, Theys J, Chiu RK, Lambin P. Hypoxia as a target for combined modality treatments. Eur J Cancer. 2002;38(2):240–57.

    Article  PubMed  CAS  Google Scholar 

  104. Boddu RS, Perumal O, Divakar K. Microbial nitroreductases: a versatile tool for biomedical and environmental applications. Biotechnol Appl Biochem. 2021;68(6):1518–30. https://doi.org/10.1002/bab.2073.

    Article  PubMed  CAS  Google Scholar 

  105. Akiva E, Copp JN, Tokuriki N, Babbitt PC. Evolutionary and molecular foundations of multiple contemporary functions of the nitroreductase superfamily. Proc Natl Acad Sci U S A. 2017;114(45):E9549-e9558.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  106. Searle PF, Chen MJ, Hu LQ, Race PR, Lovering AL, Grove JI, Guise C, Jaberipour M, James ND, Mautner V, et al. Nitroreductase: a prodrug-activating enzyme for cancer gene therapy. Clin Exp Pharmacol Physiol. 2004;31(11):811–6.

    Article  PubMed  CAS  Google Scholar 

  107. de Garibay GR, Jalon EGD, Stigen E, Lund KB, Popa M, Davidson B, Safont MM, Rygh CB, Espedal H, Barrett TM, et al. Repurposing F-18-FMISO as a PET tracer for translational imaging of nitroreductase-based gene directed enzyme prodrug therapy. Theranostics. 2021;11(12):6044–57.

    Article  CAS  Google Scholar 

  108. Qiao J, Wang M, Cui M, Fang Y, Li H, Zheng C, Li Z, Xu Y, Hua H, Li D. Small-molecule probes for fluorescent detection of cellular hypoxia-related nitroreductase. J Pharm Biomed Anal. 2021;203:114199.

    Article  PubMed  CAS  Google Scholar 

  109. Ouyang J, Sun LH, Zeng Z, Zeng C, Zeng F, Wu SZ. Nanoaggregate probe for breast cancer metastasis through multispectral optoacoustic tomography and aggregation-induced NIR-I/II fluorescence imaging. Angewandte Chemie-International Edition. 2020;59(25):10111–21.

    Article  PubMed  CAS  Google Scholar 

  110. Sun L, Ouyang J, Ma Y, Zeng Z, Zeng C, Zeng F, Wu S. An activatable probe with aggregation-induced emission for detecting and imaging herbal medicine induced liver injury with optoacoustic imaging and NIR-II fluorescence imaging. Adv Healthc Mater. 2021;10(24):e2100867. https://doi.org/10.1002/adhm.202100867.

  111. Wang XZ, Xue RF, Zhang SY, Zheng YT, Zhang LY, Jiang ZZ. Activation of natural killer T cells contributes to triptolide-induced liver injury in mice. Acta Pharmacol Sin. 2018;39(12):1847–54.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  112. Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade. Science. 2018;359(6382):1350–5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  113. Carlos-Reyes A, Muñiz-Lino MA, Romero-Garcia S, López-Camarillo C, Hernández-de la Cruz ON. Biological adaptations of tumor cells to radiation therapy. Front Oncol. 2021;11:718636. https://doi.org/10.3389/fonc.2021.718636.

  114. Gu G, Dustin D, Fuqua SA. Targeted therapy for breast cancer and molecular mechanisms of resistance to treatment. Curr Opin Pharmacol. 2016;31:97–103.

    Article  PubMed  CAS  Google Scholar 

  115. Cai Y, Si W, Huang W, Chen P, Shao J, Dong X. Organic dye based nanoparticles for cancer phototheranostics. Small. 2018;14(25):e1704247.

    Article  PubMed  CAS  Google Scholar 

  116. Chen C, Ou H, Liu R, Ding D. Regulating the photophysical property of organic/polymer optical agents for promoted cancer phototheranostics. Adv Mater. 2020;32(3):e1806331.

    Article  PubMed  CAS  Google Scholar 

  117. Dai H, Shen Q, Shao J, Wang W, Gao F, Dong X. Small molecular NIR-II fluorophores for cancer phototheranostics. Innovation (N Y). 2021;2(1):100082.

    Google Scholar 

  118. Wang S, Wang X, Yu L, Sun M. Progress and trends of photodynamic therapy: from traditional photosensitizers to AIE-based photosensitizers. Photodiagnosis and Photodynamic Therapy. 2021;34:102254.

    Article  PubMed  CAS  Google Scholar 

  119. Xiao Y-F, Chen W-C, Chen J-X, Lu G, Tian S, Cui X, Zhang Z, Chen H, Wan Y, Li S, et al. Amplifying free radical generation of AIE photosensitizer with small singlet–triplet splitting for hypoxia-overcoming photodynamic therapy. ACS Appl Mater Interfaces. 2022;14(4):5112–21.

    Article  PubMed  CAS  Google Scholar 

  120. He Z, Tian S, Gao Y, Meng F, Luo L. Luminescent AIE dots for anticancer photodynamic therapy. Front Chem. 2021;9:672917.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  121. Qi J, Ou H, Liu Q, Ding D. Gathering brings strength: how organic aggregates boost disease phototheranostics. Aggregate. 2021;2(1):95–113.

    Article  Google Scholar 

  122. Schaafsma BE, Mieog JS, Hutteman M, van der Vorst JR, Kuppen PJ, Löwik CW, Frangioni JV, van de Velde CJ, Vahrmeijer AL. The clinical use of indocyanine green as a near-infrared fluorescent contrast agent for image-guided oncologic surgery. J Surg Oncol. 2011;104(3):323–32.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  123. Hou Y-J, Yang X-X, Liu R-Q, Zhao D, Guo C-X, Zhu A-C, Wen M-N, Liu Z, Qu G-F, Meng H-X. Pathological mechanism of photodynamic therapy and photothermal therapy based on nanoparticles. Int J Nanomedicine. 2020;15:6827–38.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  124. Wei Y, Wang Z, Yang J, Xu R, Deng H, Ma S, Fang T, Zhang J, Shen Q. Reactive oxygen species / photothermal therapy dual-triggered biomimetic gold nanocages nanoplatform for combination cancer therapy via ferroptosis and tumor-associated macrophage repolarization mechanism. J Colloid Interface Sci. 2022;606(Pt 2):1950–65.

    Article  PubMed  CAS  Google Scholar 

  125. Li H, Kim H, Han J, Nguyen V-N, Peng X, Yoon J. Activity-based smart AIEgens for detection, bioimaging, and therapeutics: recent progress and outlook. Aggregate. 2021;2(4):e51.

    Google Scholar 

  126. Li X, Zhang D, Yin C, Lu G, Wan Y, Huang Z, Tan J, Li S, Luo J, Lee C-S. A diradicaloid small molecular nanotheranostic with strong near-infrared absorbance for effective cancer photoacoustic imaging and photothermal therapy. ACS Appl Mater Interfaces. 2021;13(14):15983–91.

    Article  PubMed  CAS  Google Scholar 

  127. Xu W, Wang D, Tang BZ. NIR-II AIEgens: a win-win integration towards bioapplications. Angew Chem Int Ed Engl. 2021;60(14):7476–87.

    Article  PubMed  CAS  Google Scholar 

  128. Xu Y, Zhang Y, Li J, An J, Li C, Bai S, Sharma A, Deng G, Kim JS, Sun Y. NIR-II emissive multifunctional AIEgen with single laser-activated synergistic photodynamic/photothermal therapy of cancers and pathogens. Biomaterials. 2020;259:120315. https://doi.org/10.1016/j.biomaterials.2020.120315.

    Article  PubMed  CAS  Google Scholar 

  129. Punnoose J, Nachman H, Ashkenazi S. Oxygen imaging for non-invasive metastasis detection. Sensors. 2022;22(1):237.

    Article  CAS  Google Scholar 

  130. Kwak YH, Lee YJ, Lee JY, Nam EJ, Kim S, Kim YT, Kim SW. Indocyanine green fluorescent image-guided inguinal sentinel lymph node biopsy in vulvar cancer. Obstet Gynecol Sci. 2021. https://doi.org/10.5468/ogs.21335.

  131. Chow S, Karam A. Role of sentinel lymph node biopsy for gynecologic cancers. Curr Opin Obstet Gynecol. 2022;34(1):15–9.

    Article  PubMed  Google Scholar 

  132. Cai X, Liu J, Liew WH, Duan Y, Geng J, Thakor N, Yao K, Liao L-D, Liu B. Organic molecules with propeller structures for efficient photoacoustic imaging and photothermal ablation of cancer cells. Materials Chemistry Frontiers. 2017;1(8):1556–62.

    Article  CAS  Google Scholar 

  133. Wang D, Dong H, Li M, Cao Y, Yang F, Zhang K, Dai W, Wang C, Zhang X. Erythrocyte-cancer hybrid membrane camouflaged hollow copper sulfide nanoparticles for prolonged circulation life and homotypic-targeting photothermal/chemotherapy of melanoma. ACS Nano. 2018;12(6):5241–52.

    Article  PubMed  CAS  Google Scholar 

  134. Chen W, Ouyang J, Liu H, Chen M, Zeng K, Sheng J, Liu Z, Han Y, Wang L, Li J, et al. Black phosphorus nanosheet-based drug delivery system for synergistic photodynamic/photothermal/chemotherapy of cancer. Adv Mater. 2017;29(5):1603864.

    Article  CAS  Google Scholar 

  135. Ma N, Zhang M-K, Wang X-S, Zhang L, Feng J, Zhang X-Z. NIR light-triggered degradable MoTe2 nanosheets for combined photothermal and chemotherapy of cancer. Adv Func Mater. 2018;28(31):1801139.

    Article  CAS  Google Scholar 

  136. Xiao YF, An FF, Chen JX, Yu J, Tao WW, Yu Z, Ting R, Lee CS, Zhang XH. The nanoassembly of an intrinsically cytotoxic near-infrared dye for multifunctionally synergistic theranostics. Small. 2019;15(38):e1903121. https://doi.org/10.1002/smll.201903121.

  137. Antaris AL, Chen H, Cheng K, Sun Y, Hong G, Qu C, Diao S, Deng Z, Hu X, Zhang B, et al. A small-molecule dye for NIR-II imaging. Nat Mater. 2016;15(2):235–42.

    Article  PubMed  CAS  Google Scholar 

  138. Xu WH, Zhang ZJ, Kang MM, Guo H, Li YM, Wen HF, Lee MMS, Wang ZY, Kwok RTK, Lam JWY, et al. Making the best use of excited-state energy: multimodality theranostic systems based on second near-infrared (NIR-II) aggregation-induced emission luminogens (AIEgens). Acs Materials Letters. 2020;2(8):1033–40.

    Article  CAS  Google Scholar 

  139. Liu LQ, Wang X, Wang LJ, Guo LQ, Li YB, Bai B, Fu F, Lu HG, Zhao XW. One-for-all phototheranostic agent based on aggregation-induced emission characteristics for multimodal imaging-guided synergistic photodynamic/photothermal cancer therapy. ACS Appl Mater Interfaces. 2021;13(17):19668–78.

    Article  PubMed  CAS  Google Scholar 

  140. Wen H, Zhang Z, Kang M, Li H, Xu W, Guo H, Li Y, Tan Y, Wen Z, Wu Q, Huang J, Xi L, Li K, Wang L, Wang D, Tang BZ. One-for-all phototheranostics: Single component AIE dots as multi-modality theranostic agent for fluorescence-photoacoustic imaging-guided synergistic cancer therapy. Biomaterials. 2021;274:120892. https://doi.org/10.1016/j.biomaterials.2021.120892.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This project was financially supported by the Research Grants Council of Hong Kong (16306620, N-HKUST609/19, and C6014-20W), the National Natural Science Foundation of China (21788102), the Innovation and Technology Commission (ITC-CNERC14SC01 and ITCPD/17-9), the General Program of Shenzhen Science and Technology Innovation Commission (JCYJ20190807144209381), the Shenzhen Key Medical Discipline Construction Fund (No. SZXK015) and the National Natural Youth Foundation of China (81901771).

Author information

Authors and Affiliations

  1. Department of Gastrointestinal Surgery, The Second Clinical Medical College, Jinan University (Shenzhen People’s Hospital), The First Affiliated Hospital, Southern University of Science and Technology, 518020, Shenzhen, China

    Pei Li, Yang Li & Li Gang Xia

  2. Department of Chemistry, Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration & Reconstruction, Division of Life Science, and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China

    Pei Li, Xuewen He, Jacky Wing Yip Lam, Ryan Tsz Kin Kwok & Ben Zhong Tang

  3. The First Affiliated Hospital, Jinan University, Guangzhou, 510632, China

    Pei Li & Cun Chuan Wang

  4. Department of General Surgery, Shenzhen People’s Hospital, Shenzhen, 518020, Guangdong, China

    Pei Li, Yang Li & Li Gang Xia

  5. Shenzhen Institute of Molecular Aggregate Science and Engineering, School of Science and Engineering, The Chinese University of Hong Kong, Shenzhen, 2001 Longxiang Boulevard, Longgang District, Shenzhen City, 518172, Guangdong, China

    Ben Zhong Tang

Authors
  1. Pei Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xuewen He
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yang Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jacky Wing Yip Lam
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ryan Tsz Kin Kwok
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Cun Chuan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Li Gang Xia
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ben Zhong Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Pei Li and Ryan Tsz Kin Kwok had the idea for the article. Pei Li performed article search and selection, analyzed the data, and drafted the manuscript. Yang Li gave support during study search and selection. Jacky Wing Yip Lam, Cun Chuan Wang, Li Gang Xia, and Ben Zhong Tang conceptualized the study and coordinated the study workflow. Xue Wen He and Ryan Tsz Kin Kwok critically reviewed the manuscript. All the authors reviewed the final version of the text.

Corresponding authors

Correspondence to Ryan Tsz Kin Kwok, Cun Chuan Wang or Li Gang Xia.

Ethics declarations

Ethics approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher’s note

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

This article is part of the Topical Collection on Preclinical Imaging.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, P., He, X., Li, Y. et al. Recent advances in aggregation-induced emission luminogens in photoacoustic imaging. Eur J Nucl Med Mol Imaging 49, 2560–2583 (2022). https://doi.org/10.1007/s00259-022-05726-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-022-05726-8

Keywords

Search

Navigation