Abstract
Purpose
Aggregation-induced emission (AIE) molecules have been widely utilized for fluorescence imaging in many biomedical applications, benefited from large Stokes shift, high quantum yield, good biocompatibility, and resistance to photobleaching. And visualization of mitochondria is almost investigated in vitro and ex vivo, but in vivo study of mitochondria is more essential for systematic biological research, especially during embryogenesis. Therefore, suitable and time-saving alternatives with simple operation based on AIE molecules are urgently needed compared with traditional transgenic approach.
Procedures
Five tetraphenylethylene isoquinolinium (TPE-IQ)-based molecules with AIE characteristics and their ability of mitochondrial visualization in vitro and in vivo and mitochondrial tracking during embryogenesis on zebrafish model were investigated. The biosafety of these AIE molecules was also evaluated systematically in vitro and in vivo.
Results
All these five AIE molecules could image mitochondria in vitro with good biocompatibility. In them, TPE-IQ1 exhibited excellent imaging quality for in vivo visualization and tracking of mitochondria during the 4-day embryogenesis in zebrafish, in comparison with the conventional transgenic fluorescent protein. Furthermore, TPE-IQ1 could visualize mitochondrial damage induced by chemicals in real time on 24-h post fertilization (hpf) embryos.
Conclusions
This study indicated TPE-IQ-based AIE molecules had the potential for mitochondrial imaging and tracking during embryogenesis and mitochondrial damage visualization in vivo.
Similar content being viewed by others
References
Lv F, Liu DP, Zheng WH, Zhao YL, Song FL (2021) BOPHY-based aggregation-induced-emission nanoparticle photosensitizers for photodynamic therapy. Acs Appl Nano Mater 4:6012–6019
Luo J, Xie Z, Lam JW, et al. (2001) Aggregation-induced emission of 1-methyl-1,2,3,4,5-pentaphenylsilole. Chem Commun (Camb) 18:1740–1741
Lim S, Tang BZ, Hong YN (2015) AIE luminogens for visualizing cell structures and functions [abstract]. ACS Symp Ser 1227:199-216P
Hong Y, Lam JW, Tang BZ (2009) Aggregation-induced emission: phenomenon, mechanism and applications. Chem Commun (Camb) 29:4332–4353
Mei J, Hong Y, Lam JW, Qin A, Tang Y, Tang BZ (2014) Aggregation-induced emission: the whole is more brilliant than the parts. Adv Mater 26:5429–5479
Mei J, Leung NL, Kwok RT, Lam JW, Tang BZ (2015) Aggregation-induced emission: together we shine, united we soar! Chem Rev 115:11718–11940
Sheng Z, Li Y, Hu D et al (2020) Centimeter-deep NIR-II fluorescence imaging with nontoxic AIE probes in nonhuman primates. Research 2020:4074593
Nunnari J, Suomalainen A (2012) Mitochondria: in sickness and in health. Cell 148:1145–1159
Zong WX, Rabinowitz JD, White E (2016) Mitochondria and cancer. Mol Cell 61:667–676
Rovira-Llopis S, Bañuls C, Diaz-Morales N, Hernandez-Mijares A, Rocha M, Victor VM (2017) Mitochondrial dynamics in type 2 diabetes: pathophysiological implications. Redox Biol 11:637–645
Lin MT, Beal MF (2006) Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443:787–795
Winata CL, Dodzian J, Bialek-Wyrzykowska U (2020) The zebrafish as a model for developmental and biomedical research in Poland and beyond. Dev Biol 457:167–168
Mork L, Crump G (2015) Zebrafish craniofacial development: a window into early patterning. Curr Top Dev Biol 115:235–269
Gore AV, Pillay LM, VeneroGalanternik M, Weinstein BM (2018) The zebrafish: a fintastic model for hematopoietic development and disease. Wiley Interdiscip Rev Dev Biol 7:e312
Outtandy P, Russell C, Kleta R, Bockenhauer D (2019) Zebrafish as a model for kidney function and disease. Pediatr Nephrol 34:751–762
Azevedo RDS, Falcão KVG, Amaral IPG, Leite ACR, Bezerra RS (2020) Mitochondria as targets for toxicity and metabolism research using zebrafish. Biochim Biophys Acta Gen Subj 1864:129634
Kim MJ, Kang KH, Kim CH, Choi SY (2008) Real-time imaging of mitochondria in transgenic zebrafish expressing mitochondrially targeted GFP. Biotechniques 45:331–334
Huang Y, Zhang P, Gao M et al (2016) Ratiometric detection and imaging of endogenous hypochlorite in live cells and in vivo achieved by using an aggregation induced emission (AIE)-based nanoprobe. Chem Commun (Camb) 52:7288–7291
Wang Y, Wu X, Cheng Y, Zhao X (2016) A fluorescent switchable AIE probe for selective imaging of dipeptidyl peptidase-4 in vitro and in vivo and its application in screening DPP-4 inhibitors. Chem Commun (Camb) 52:3478–3481
Gui S, Huang Y, Hu F et al (2018) Bioinspired peptide for imaging Hg(2+) distribution in living cells and zebrafish based on coordination-mediated supramolecular assembling. Anal Chem 90:9708–9715
Zhou Y, Gu Z, Liu C et al (2022) A polymeric nanobeacon for monitoring the fluctuation of hydrogen polysulfides during fertilization and embryonic development. Angew Chem Int Ed Engl 61:e202114504
Manghnani PN, Wu W, Xu S, Hu F, Teh C, Liu B (2018) Visualizing photodynamic therapy in transgenic zebrafish using organic nanoparticles with aggregation-induced emission. Nanomicro Lett 10:61
Wang S, Wu W, Manghnani P et al (2019) Polymerization-enhanced two-photon photosensitization for precise photodynamic therapy. ACS Nano 13:3095–3105
Chen S, Cui S, Du R et al (2018) Simultaneous near-infrared and green fluorescence from single conjugated polymer dots with aggregation-induced emission fluorogen for cell imaging. J Mater Chem B 6:7871–7876
Tsai WK, Wang CI, Liao CH et al (2019) Molecular design of near-infrared fluorescent Pdots for tumor targeting: aggregation-induced emission versus anti-aggregation-caused quenching. Chem Sci 10:198–207
Xu C, Peng C, Yang X et al (2022) One-pot synthesis of customized metal-phenolic-network-coated AIE dots for in vivo bioimaging. Adv Sci (Weinh) 9:e2104997
Liu MX, Ma LL, Liu XY et al (2019) Combination of [12]aneN3 and triphenylamine-benzylideneimidazolone as nonviral gene vectors with two-photon and AIE properties. ACS Appl Mater Interf 11:42975–42987
Hu F, Manghnani PN, Kenry et al (2019) Visualize embryogenesis and cell fate using fluorescent probes with aggregation-induced emission. ACS Appl Mater Interfaces 11:3737–3744
Zhou Y, Gu Z, Liu C et al (2022) A polymeric nanobeacon for monitoring the fluctuation of hydrogen polysulfides during fertilization and embryonic development. Angew Chem Int Ed Engl 61:e202114504
Hu F, Cai X, Manghnani PN, Kenry WuW, Liu B (2018) Multicolor monitoring of cellular organelles by single wavelength excitation to visualize the mitophagy process. Chem Sci 9:2756–2761
Dai Y, He F, Ji H, Zhao X, Misal S, Qi Z (2020) Dual-functional NIR AIEgens for high-fidelity imaging of lysosomes in cells and photodynamic therapy. ACS Sens 5:225–233
Li N, Liu L, Luo H, Wang H, Yang D, He F (2020) Flavanone-based fluorophores with aggregation-induced emission enhancement characteristics for mitochondria-imaging and zebrafish-imaging. Molecules 25:3298
Shi L, Liu YH, Li K et al (2020) An AIE-based probe for rapid and ultrasensitive imaging of plasma membranes in biosystems. Angew Chem Int Ed Engl 59:9962–9966
Zhao N, Ma C, Yang W, Yin W, Wei J, Li N (2019) Facile construction of boranil complexes with aggregation-induced emission characteristics and their specific lipid droplet imaging applications. Chem Commun (Camb) 55:8494–8497
Luo H, Li N, Liu L, Wang H, He F (2021) Synthesis of new AIEE-active chalcones for imaging of mitochondria in living cells and zebrafish in vivo. Int J Mol Sci 22:8949
Zhao E, Deng H, Chen S et al (2014) A dual functional AEE fluorogen as a mitochondrial-specific bioprobe and an effective photosensitizer for photodynamic therapy. Chem Commun (Camb) 50:14451–14454
Gui C, Zhao E, Kwok RTK et al (2017) AIE-active theranostic system: selective staining and killing of cancer cells. Chem Sci 8:1822–1830
Capriello T, Grimaldi MC, Cofone R, D’Aniello S, Ferrandino I (2019) Effects of aluminium and cadmium on hatching and swimming ability in developing zebrafish. Chemosphere 222:243–249
Schindelin J, Arganda-Carreras I, Frise E et al (2012) Fiji: an open-source platform for biological-image analysis. Nat Methods 9:676–682
Chen K, Zhang R, Wang Z, Zhang W, Tang BZ (2020) Structural modification orientated multifunctional AIE fluorescence probes: organelles imaging and effective photosensitizer for photodynamic therapy. Advanced Optical Materials 8:1901433
Brinkmann BW, Beijk WF, Vlieg RC et al (2021) Adsorption of titanium dioxide nanoparticles onto zebrafish eggs affects colonizing microbiota. Aquat Toxicol 232:105744
Halbach K, Ulrich N, Goss KU et al (2020) Yolk sac of zebrafish embryos as backpack for chemicals? Environ Sci Technol 54:10159–10169
Sant KE, Timme-Laragy AR (2018) Zebrafish as a model for toxicological perturbation of yolk and nutrition in the early embryo. Curr Environ Health Rep 5:125–133
Wei Y, Meng Y, Huang Y et al (2021) Development toxicity and cardiotoxicity in zebrafish from exposure to iprodione. Chemosphere 263:127860
Xu Z, Ni H, Huang Y et al (2020) Effect of fomesafen on the embryonic development of zebrafish. Chemosphere 259:127380
Ding X, Zhu J, Zhang J et al (2020) Developmental toxicity of disinfection by-product monohaloacetamides in embryo-larval stage of zebrafish. Ecotoxicol Environ Saf 189:110037
Köktürk M, Altindağ F, Ozhan G, Çalimli MH, Nas MS (2021) Textile dyes Maxilon blue 5G and Reactive blue 203 induce acute toxicity and DNA damage during embryonic development of Danio rerio. Comp Biochem Physiol C Toxicol Pharmacol 242:108947
Kane MS, Paris A, Codron P et al (2018) Current mechanistic insights into the CCCP-induced cell survival response. Biochem Pharmacol 148:100–110
Yin J, Guo J, Zhang Q et al (2018) Doxorubicin-induced mitophagy and mitochondrial damage is associated with dysregulation of the PINK1/parkin pathway. Toxicol In Vitro 51:1–10
Kang L, Liu S, Li J, Tian Y, Xue Y, Liu X (2020) The mitochondria-targeted anti-oxidant MitoQ protects against intervertebral disc degeneration by ameliorating mitochondrial dysfunction and redox imbalance. Cell Prolif 53:e12779
Rizwan H, Pal S, Sabnam S, Pal A (2020) High glucose augments ROS generation regulates mitochondrial dysfunction and apoptosis via stress signalling cascades in keratinocytes. Life Sci 241:117148
Tian M, He X, Jin C et al (2021) Transpathology: molecular imaging-based pathology. Eur J Nucl Med Mol Imaging 48:2338–2350
Acknowledgements
We thank Weijun Pan from the Shanghai Institute of Nutrition and Health, CAS for the kind support.
Funding
This study was funded by the National Natural Science Foundation of China (21788102, 81725009, 82030049, 32027802), the National Key R&D Program of China (2021YFE0108300, 2021YFA1101700), and the Fundamental Research Funds for the Central Universities: 2021FZZX002-05.
Author information
Authors and Affiliations
Contributions
In this work, Peili Cen, Hong Zhang, and Mei Tian conceived the study and coordinated the experiments. Peili Cen performed and participated in the whole experiment and wrote the manuscript. Chunyi Cui participated in zebrafish experiments. Yan Zhong and Youyou Zhou participated in cell experiments. Zhiming Wang provided materials. Pengfei Xu provided zebrafish line and experimental conditions. Chunyi Cui, Xiaoyun Luo, and Le Xue participated in the data analysis. Zhen Cheng, Yen Wei, and Qinggang He gave suggestions and modified the manuscript in the preparation and revision. And all authors agree with the content of manuscript.
Corresponding authors
Ethics declarations
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.
Supplementary Information
Below is the link to the electronic supplementary material.
Supplementary file2 (AVI 1594 KB)
Rights and permissions
About this article
Cite this article
Cen, P., Cui, C., Zhong, Y. et al. Visualization of Mitochondria During Embryogenesis in Zebrafish by Aggregation-Induced Emission Molecules. Mol Imaging Biol 24, 1007–1017 (2022). https://doi.org/10.1007/s11307-022-01752-y
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11307-022-01752-y