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Fluorescent Quantum Dots, A Technological Marvel for Optical Bio-imaging: A Perspective on Associated In Vivo Toxicity

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Application of Quantum Dots in Biology and Medicine

Abstract

Semiconductor quantum dots (QDs) are one of the technological wonders, known for their excellent photo-physical properties. The recent advances in nanotechnology have made QDs a robust and readily available fluorescent probe for both in vitro and in vivo bio-imaging research. QDs offer great advantages over traditional organic fluorescent dyes and present a number of beneficial characteristics such as size-tunable emission spectra, signal brightness, long life time, photostability, longer multiphoton cross sectioning capabilities and so on. Since its inception, it is being used as excellent fluorescent probe for a wide range of fluorescence microscopy technologies ranging from conventional epifluorescence, confocal, multiphoton to super-resolution microscopy for in vitro cell and tissue imaging to in vivo deep tissue and whole animal imaging. Hence, QDs have opened up plethora of exciting possibilities in bio-imaging research by enabling the researchers to probe and visualize the invisible biological processes from the whole organism level (macroscale) down to the cellular and in molecular level (nanoscale). Despite its enormous potential in bio-imaging, the involvement of heavy metals and the colloidal instability of QDs have led to legitimate concerns about toxicity. These issues have impeded the widespread adoption of QDs, especially in biomedical and in vivo bio-imaging. This chapter mainly focuses on the QD-based fluorescence bio-imaging applications from biological point of view and discuss relevant toxicity issues associated with using QDs in in vivo investigations.

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References

  1. Zimmer M. GFP: from jellyfish to the Nobel prize and beyond. Chem Soc Rev. 2009;38(10).

    Google Scholar 

  2. Chudakov DM, Lukyanov S, Lukyanov KA. Fluorescent proteins as a toolkit for in vivo imaging. Trends Biotechnol. 2005;23.

    Google Scholar 

  3. Wegner KD, Hildebrandt N. Quantum dots: bright and versatile in vitro and in vivo fluorescence imaging biosensors. Chem Soc Rev. 2015;44.

    Google Scholar 

  4. Drummen GPC. Quantum dots—from synthesis to applications in biomedicine and life sciences. Int J Mol Sci. 2010;11.

    Google Scholar 

  5. van Driel AF, Allan G, Delerue C, Lodahl P, Vos WL, Vanmaekelbergh D. Frequency-dependent spontaneous emission rate from CdSe and CdTe nanocrystals: influence of dark states. Phys Rev Lett. 2005;95(23).

    Google Scholar 

  6. Mitchell AC, Dad S, Morgan CG. Selective detection of luminescence from semiconductor quantum dots by nanosecond time-gated imaging with a colour-masked CCD detector. J Microsc. 2008;230(2):172–6.

    Google Scholar 

  7. Han M, Gao X, Su JZ, Nie S. Quantum-dot-tagged microbeads for multiplexed optical coding of biomolecules. Nat Biotechnol. 2001;19(7).

    Google Scholar 

  8. Bentolila LA, Ebenstein Y, Weiss S. Quantum dots for in vivo small-animal imaging. J Nucl Med. 2009;50.

    Google Scholar 

  9. Wu X, Liu H, Liu J, Haley KN, Treadway JA, Larson JP, et al. Immunofluorescent labeling of cancer marker Her2 and other cellular targets with semiconductor quantum dots. Nat Biotechnol. 2003;21(1).

    Google Scholar 

  10. Medintz IL, Mattoussi H. Quantum dot-based resonance energy transfer and its growing application in biology. Phys Chem Chem Phys. 2009;11.

    Google Scholar 

  11. Ishikawa-Ankerhold HC, Ankerhold R, Drummen GPC. Advanced fluorescence microscopy techniques-FRAP, FLIP, FLAP, FRET and FLIM. Molecules. 2012;17.

    Google Scholar 

  12. Algar WR, Susumu K, Delehanty JB, Medintz IL. Semiconductor quantum dots in bioanalysis: crossing the valley of death. Anal Chem. 2011;83(23).

    Google Scholar 

  13. Bruchez M, Moronne M, Gin P, Weiss S, Alivisatos AP. Semiconductor nanocrystals as fluorescent biological labels. Science. 1998;281(5385).

    Google Scholar 

  14. Chan WCW, Nie S. Quantum dot bioconjugates for ultrasensitive nonisotopic detection. Science. 1998;281(5385).

    Google Scholar 

  15. Xiao Y, Barker PE. Semiconductor nanocrystal probes for human metaphase chromosomes. Nucleic Acids Res. 2004;32(3).

    Google Scholar 

  16. Li X, Yan Z, Xiao J, Liu G, Li Y, Xiu Y. Cytotoxicity of CdSe quantum dots and corresponding comparison with FITC in cell imaging efficiency. Int J Clin Exp Med. 2017;10(1).

    Google Scholar 

  17. Delehanty JB, Mattoussi H, Medintz IL. Delivering quantum dots into cells: strategies, progress and remaining issues. Anal Bioanal Chem. 2009;393.

    Google Scholar 

  18. Qian J, Yong KT, Roy I, Ohulchanskyy TY, Bergey EJ, Lee BH, et al. Imaging pancreatic cancer using surface-functionalized quantum dots. J Phys Chem B. 2007;111(25).

    Google Scholar 

  19. Bailey RE, Smith AM, Nie S. Quantum dots in biology and medicine. Phys E Low-Dimension Syst Nanostruct. 2004;25.

    Google Scholar 

  20. Palmieri V, Papi M, Conti C, Ciasca G, Maulucci G, de Spirito M. The future development of bacteria fighting medical devices: the role of graphene oxide. Expert Rev Med Dev. 2016;13.

    Google Scholar 

  21. Bacon M, Bradley SJ, Nann T. Graphene quantum dots. In: Particle and particle systems characterization, vol. 1. Germany: Wiley-VCH Verlag; 2014. p. 415–28.

    Google Scholar 

  22. Åkerman ME, Chan WCW, Laakkonen P, Bhatia SN, Ruoslahti E. Nanocrystal targeting in vivo. Proc Nat Acad Sci USA. 2002;99(20).

    Google Scholar 

  23. Larson DR, Zipfel WR, Williams RM, Clark SW, Bruchez MP, Wise FW, et al. Water-soluble quantum dots for multiphoton fluorescence imaging in vivo. Science. 2003;300(5624).

    Google Scholar 

  24. Bharali DJ, Lucey DW, Jayakumar H, Pudavar HE, Prasad PN. Folate-receptor-mediated delivery of InP quantum dots for bioimaging using confocal and two-photon microscopy. J Am Chem Soc. 2005;127(32).

    Google Scholar 

  25. Xu G, Yong KT, Roy I, Mahajan SD, Ding H, Schwartz SA, et al. Bioconjugated quantum rods as targeted probes for efficient transmigration across an in vitro blood-brain barrier. Bioconjug Chem. 2008;19(6).

    Google Scholar 

  26. Belyaeva TN, Salova AV, Leontieva EA, Mozhenok TP, Kornilova ES, Krolenko SA. Untargeted quantum dots in confocal microscopy of living cells. Cell Tissue Biol. 2009;3(6).

    Google Scholar 

  27. Yukawa H, Watanabe M, Kaji N, Okamoto Y, Tokeshi M, Miyamoto Y, et al. Monitoring transplanted adipose tissue-derived stem cells combined with heparin in the liver by fluorescence imaging using quantum dots. Biomaterials. 2012;33(7).

    Google Scholar 

  28. Yukawa H, Watanabe M, Kaji N, Baba Y. Influence of autofluorescence derived from living body on in vivo fluorescence imaging using quantum dots. Cell Med. 2015;7(2).

    Google Scholar 

  29. Huang N, Cheng S, Zhang X, Tian Q, Pi J, Tang J, et al. Efficacy of NGR peptide-modified PEGylated quantum dots for crossing the blood–brain barrier and targeted fluorescence imaging of glioma and tumor vasculature. Nanomed Nanotechnol Biol Med. 2017;13(1).

    Google Scholar 

  30. Wang H, Yang H, Xu ZP, Liu X, Roberts MS, Liang X. Anionic long-circulating quantum dots for long-term intravital vascular imaging. Pharmaceutics. 2018;10(4).

    Google Scholar 

  31. Liu H, Deng X, Tong S, He C, Cheng H, Zhuang Z, et al. In vivo deep-brain structural and hemodynamic multiphoton microscopy enabled by quantum dots. Nano Lett. 2019;19(8).

    Google Scholar 

  32. Alivisatos AP, Gu W, Larabell C. Quantum dots as cellular probes. Ann Rev Biomed Eng. 2005;7.

    Google Scholar 

  33. Gao X, Nie S. Molecular profiling of single cells and tissue specimens with quantum dots. Trends Biotechnol. 2003;21.

    Google Scholar 

  34. Gao X, Cui Y, Levenson RM, Chung LWK, Nie S. In vivo cancer targeting and imaging with semiconductor quantum dots. Nat Biotechnol. 2004;22(8).

    Google Scholar 

  35. Maestro LM, Rodríguez EM, Rodríguez FS, de la Cruz MCI, Juarranz A, Naccache R, et al. CdSe quantum dots for two-photon fluorescence thermal imaging. Nano Lett. 2010;10(12).

    Google Scholar 

  36. Podgorski K, Ranganathan G. Brain heating induced by near-infrared lasers during multiphoton microscopy. J Neurophysiol. 2016;116(3).

    Google Scholar 

  37. Liu L, Jin S, Hu Y, Gu Z, Wu HC. Application of quantum dots in biological imaging. J Nanomater. 2011;2011.

    Google Scholar 

  38. Bera D, Qian L, Tseng TK, Holloway PH. Quantum dots and their multimodal applications: a review. Materials. 2010;3.

    Google Scholar 

  39. Dahan M, Laurence T, Pinaud F, Chemla DS, Alivisatos AP, Sauer M, et al. Time-gated biological imaging by use of colloidal quantum dots. Opt Lett. 2001;26(11).

    Google Scholar 

  40. Michalet X, Pinaud F, Lacoste TD, Dahan M, Bruchez MP, Alivisatos AP, et al. Properties of fluorescent semiconductor nanocrystals and their application to biological labeling. Single Mol. 2001;2.

    Google Scholar 

  41. Lounis B, Bechtel HA, Gerion D, Alivisatos P, Moerner WE. Photon antibunching in single CdSe/ZnS quantum dot fluorescence. Chem Phys Lett. 2000;329(5–6).

    Google Scholar 

  42. Meng HM, Zhao D, Li N, Chang J. A graphene quantum dot-based multifunctional two-photon nanoprobe for the detection and imaging of intracellular glutathione and enhanced photodynamic therapy. Analyst. 2018;143(20).

    Google Scholar 

  43. Rayleigh XV. On the theory of optical images, with special reference to the microscope. Lond Edinb Dublin Philos Mag J Sci. 1896;42(255).

    Google Scholar 

  44. Gustafsson MGL. Surpassing the lateral resolution limit by a factor of two using structured illumination microscopy. J Microsc. 2000;198(2).

    Google Scholar 

  45. Gustafsson MGL. Nonlinear structured-illumination microscopy: wide-field fluorescence imaging with theoretically unlimited resolution. Proc Nat Acad Sci USA. 2005;102(37).

    Google Scholar 

  46. Betzig E, Patterson GH, Sougrat R, Lindwasser OW, Olenych S, Bonifacino JS, et al. Imaging intracellular fluorescent proteins at nanometer resolution. Science. 2006;313(5793).

    Google Scholar 

  47. Rust MJ, Bates M, Zhuang X. Sub-diffraction-limit imaging by stochastic optical reconstruction microscopy (STORM). Nat Methods. 2006;3(10).

    Google Scholar 

  48. Huang B, Wang W, Bates M, Zhuang X. Three-dimensional super-resolution imaging by stochastic optical reconstruction microscopy. Science. 2008;319(5864).

    Google Scholar 

  49. Meyer L, Wildanger D, Medda R, Punge A, Rizzoli SO, Donnert G, et al. Dual-color STED microscopy at 30-nm focal-plane resolution. Small. 2008;4(8).

    Google Scholar 

  50. Hein B, Willig KI, Hell SW. Stimulated emission depletion (STED) nanoscopy of a fluorescent protein-labeled organelle inside a living cell. Proc Nat Acad Sci USA. 2008;105(38).

    Google Scholar 

  51. Wildanger D, Medda R, Kastrup L, Hell SW. A compact STED microscope providing 3D nanoscale resolution. J Microsc. 2009;236(1).

    Google Scholar 

  52. Hanne J, Falk HJ, Görlitz F, Hoyer P, Engelhardt J, Sahl SJ, et al. STED nanoscopy with fluorescent quantum dots. Nat Commun. 2015;6.

    Google Scholar 

  53. Yang X, Zhanghao K, Wang H, Liu Y, Wang F, Zhang X, et al. Versatile application of fluorescent quantum dot labels in super-resolution fluorescence microscopy. ACS Photonics. 2016;3(9).

    Google Scholar 

  54. Zhao M, Ye S, Peng X, Song J, Qu J. Green emitted CdSe@ZnS quantum dots for FLIM and STED imaging applications. J Innov Opt Health Sci. 2019;12(5).

    Google Scholar 

  55. Ye S, Guo J, Song J, Qu J. Achieving high-resolution of 21 nm for STED nanoscopy assisted by CdSe@ZnS quantum dots. Appl Phys Lett. 2020;116(4).

    Google Scholar 

  56. Ye S, Yan W, Zhao M, Peng X, Song J, Qu J. Low-saturation-intensity, high-photostability, and high-resolution STED nanoscopy assisted by CsPbBr3 quantum dots. Adv Mater. 2018;30(23).

    Google Scholar 

  57. Killingsworth MC, Lai K, Wu X, Yong JLC, Lee CS. Quantum dot immunocytochemical localization of somatostatin in somatostatinoma by widefield epifluorescence, superresolution light, and immunoelectron microscopy. J Histochem Cytochem. 2012;60(11).

    Google Scholar 

  58. Hess ST, Girirajan TPK, Mason MD. Ultra-high resolution imaging by fluorescence photoactivation localization microscopy. Biophys J. 2006;91(11).

    Google Scholar 

  59. Pereira PM, Almada P, Henriques R. High-content 3D multicolor super-resolution localization microscopy. Methods Cell Biol. 2015;125.

    Google Scholar 

  60. Waldchen S, Lehmann J, Klein T, van de Linde S, Sauer M. Light-induced cell damage in live-cell super-resolution microscopy. Sci Rep. 2015;5.

    Google Scholar 

  61. Nirmal M, Dabbousi BO, Bawendi MG, Macklin JJ, Trautman JK, Harris TD, et al. Fluorescence intermittency in single cadmium selenide nanocrystals. Nature. 1996;383(6603).

    Google Scholar 

  62. Urban JM, Chiang W, Hammond JW, Cogan NMB, Litzburg A, Burke R, et al. Quantum dots for improved single-molecule localization microscopy. J Phys Chem B. 2021;125(10).

    Google Scholar 

  63. Brkić S. Applicability of quantum dots in biomedical science. In: Ionizing radiation effects and applications. 2018.

    Google Scholar 

  64. Hardman R. A toxicologic review of quantum dots: toxicity depends on physicochemical and environmental factors. Environ Health Perspect. 2006;114.

    Google Scholar 

  65. Dubertret B, Skourides P, Norris DJ, Noireaux V, Brivanlou AH, Libchaber A. In vivo imaging of quantum dots encapsulated in phospholipid micelles. Science. 2002;298(5599).

    Google Scholar 

  66. Kim S, Lim YT, Soltesz EG, de Grand AM, Lee J, Nakayama A, et al. Near-infrared fluorescent type II quantum dots for sentinel lymph node mapping. Nat Biotechnol. 2004;22(1).

    Google Scholar 

  67. Hoshino A, Hanaki KI, Suzuki K, Yamamoto K. Applications of T-lymphoma labeled with fluorescent quantum dots to cell tracing markers in mouse body. Biochem Biophys Res Commun. 2004;314(1).

    Google Scholar 

  68. Ballou B, Lagerholm BC, Ernst LA, Bruchez MP, Waggoner AS. Noninvasive imaging of quantum dots in mice. Bioconjug Chem. 2004;15(1).

    Google Scholar 

  69. Jaiswal JK, Mattoussi H, Mauro JM, Simon SM. Long-term multiple color imaging of live cells using quantum dot bioconjugates. Nat Biotechnol. 2003;21(1).

    Google Scholar 

  70. Lovrić J, Cho SJ, Winnik FM, Maysinger D. Unmodified cadmium telluride quantum dots induce reactive oxygen species formation leading to multiple organelle damage and cell death. Chem Biol. 2005;12(11).

    Google Scholar 

  71. Zhu Y, Li Z, Chen M, Cooper HM, Lu GQ, Xu ZP. One-pot preparation of highly fluorescent cadmium telluride/cadmium sulfide quantum dots under neutral-pH condition for biological applications. J Colloid Interface Sci. 2013;390(1).

    Google Scholar 

  72. Medintz IL, Uyeda HT, Goldman ER, Mattoussi H. Quantum dot bioconjugates for imaging, labelling and sensing. Nat Mater. 2005;4.

    Google Scholar 

  73. Kirchner C, Liedl T, Kudera S, Pellegrino T, Javier AM, Gaub HE, et al. Cytotoxicity of colloidal CdSe and CdSe/ZnS nanoparticles. Nano Lett. 2005;5(2).

    Google Scholar 

  74. Tsay JM, Michalet X. New light on quantum dot cytotoxicity. Chem Biol. 2005;12.

    Google Scholar 

  75. Derfus AM, Chan WCW, Bhatia SN. Probing the cytotoxicity of semiconductor quantum dots. Nano Lett. 2004;4(1).

    Google Scholar 

  76. Cho SJ, Maysinger D, Jain M, Röder B, Hackbarth S, Winnik FM. Long-term exposure to CdTe quantum dots causes functional impairments in live cells. Langmuir. 2007;23(4).

    Google Scholar 

  77. Qu G, Wang X, Wang Z, Liu S, Jiang G. Cytotoxicity of quantum dots and graphene oxide to erythroid cells and macrophages. Nanoscale Res Lett. 2013;8(1).

    Google Scholar 

  78. Haque MM, Im HY, Seo JE, Hasan M, Woo K, Kwon OS. Acute toxicity and tissue distribution of CdSe/CdS-MPA quantum dots after repeated intraperitoneal injection to mice. J Appl Toxicol. 2013;33(9).

    Google Scholar 

  79. Nikazar S, Sivasankarapillai VS, Rahdar A, Gasmi S, Anumol PS, Shanavas MS. Revisiting the cytotoxicity of quantum dots: an in-depth overview. Biophys Rev. 2020;12.

    Google Scholar 

  80. Jin S, Hu Y, Gu Z, Liu L, Wu H-C. Application of quantum dots in biological imaging. J Nanomater. 2011;2011:13.

    Article  Google Scholar 

  81. Yong K-T, Ding H, Roy I, Law W-C, Bergey EJ, Maitra A, et al. Imaging pancreatic cancer using bioconjugated InP quantum dots. 2009. Available from: www.acsnano.org.

  82. Zhang S, Jiang Y, Chen CS, Spurgin J, Schwehr KA, Quigg A, et al. Aggregation, dissolution, and stability of quantum dots in marine environments: importance of extracellular polymeric substances. Environ Sci Technol. 2012;46(16).

    Google Scholar 

  83. Rocha TL, Mestre NC, Sabóia-Morais SMT, Bebianno MJ. Environmental behaviour and ecotoxicity of quantum dots at various trophic levels: a review. Environ Int. 2017;98.

    Google Scholar 

  84. Derivery E, Bartolami E, Matile S, Gonzalez-Gaitan M. Efficient delivery of quantum dots into the cytosol of cells using cell-penetrating poly(disulfide)s. J Am Chem Soc. 2017;139(30).

    Google Scholar 

  85. Ahmed S, Nakaji-Hirabayashi T, Rajan R, Zhao D, Matsumura K. Cytosolic delivery of quantum dots mediated by freezing and hydrophobic polyampholytes in RAW 264.7 cells. J Mater Chem B. 2019;7(46).

    Google Scholar 

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Acknowledgements

The author wishes to thank Prof. Aurnab Ghose, IISER Pune for reading the manuscript and valuable inputs.

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  1. Indian Institute of Science Education and Research (IISER) Pune, Dr. Homi Bhabha Road, Pune, 411008, India

    Santosh Podder

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Correspondence to Santosh Podder .

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  1. S. N. Bose National Centre for Basic Sciences, Kolkata, West Bengal, India

    Puspendu Barik

  2. Department of Chemistry, Rammohan College, University of Calcutta, Kolkata, West Bengal, India

    Samiran Mondal

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Podder, S. (2022). Fluorescent Quantum Dots, A Technological Marvel for Optical Bio-imaging: A Perspective on Associated In Vivo Toxicity. In: Barik, P., Mondal, S. (eds) Application of Quantum Dots in Biology and Medicine. Springer, Singapore. https://doi.org/10.1007/978-981-19-3144-4_8

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