Abstract
The authors describe the synthesis of water-soluble and fluorescent graphene oxide quantum dots via acid exfoliation of graphite nanoparticles. The resultant graphene oxide quantum dots (GoQDs) were then modified with folic acid. Folic acid receptors are overexpressed in cancer cells and hence can bind to functionalized graphene oxide quantum dots. On excitation at 305 nm, the GoQDs display green fluorescence with a peak wavelength at ~520 nm. The modified GoQDs are non-toxic to macrophage cells even after prolonged exposure and high concentrations. Fluorescence lifetime imaging and multiphoton microscopy was used (in combination) to image HeCaT cells exposed to GoQDs, resulting in a superior method for bioimaging.
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References
Weissleder R, Pittet MJ (2008) Imaging in the era of molecular oncology. Nature 452:580–589. https://doi.org/10.1038/nature06917
Wang D, Chen J-F, Dai L (2015) Recent advances in graphene quantum dots for fluorescence bioimagin from cells through tissues to animals. Part Part Syst Charact 32:515–523
Fan Z, Li S, Yuan F, Fan L (2015) Fluorescent graphene quantum dots for biosensing and bioimaging. RSC Adv 5:19773–19789. https://doi.org/10.1039/C4RA17131D
Zhou J, Zhou H, Tang J et al (2017) Carbon dots doped with heteroatoms for fluorescent bioimaging: a review. Microchim Acta 184:343–368. https://doi.org/10.1007/s00604-016-2043-9
Zhang M, Wang J, Wang W et al (2017) Magnetofluorescent photothermal micelles packaged with GdN@CQDs as photothermal and chemical dual-modal therapeutic agents. Chem Eng J 330:442–452. https://doi.org/10.1016/j.cej.2017.07.138
Zhang M, Wang W, Yuan P et al (2017) Synthesis of lanthanum doped carbon dots for detection of mercury ion, multi-color imaging of cells and tissue, and bacteriostasis. Chem Eng J 330:1137–1147. https://doi.org/10.1016/j.cej.2017.07.166
Sun A, Mu L, Hu X (2017) Graphene oxide quantum dots as novel nanozymes for alcohol intoxication. ACS Appl Mater Interfaces 9:12241–12252. https://doi.org/10.1021/acsami.7b00306
Derfus AM, Chan WCW, Bhatia SN (2004) Probing the cytotoxicity of semiconductor quantum dots. Nano Lett 4:11–18
Clift MJD, Varet J, Hankin SM et al (2011) Quantum dot cytotoxicity in vitro: an investigation into the cytotoxic effects of a series of different surface chemistries and their core/shell materials. Nanotoxicology 5:664–674. https://doi.org/10.3109/17435390.2010.534196
Clift MJD, Boyles MSP, Brown DM, Stone V (2010) An investigation into the potential for different surface-coated quantum dots to cause oxidative stress and affect macrophage cell signalling in vitro. Nanotoxicology 4:139–149. https://doi.org/10.3109/17435390903276925
Schroeder KL, Goreham RV, Nann T (2016) Graphene quantum dots for theranostics and bioimaging. Pharm Res 33:2337–2357. https://doi.org/10.1007/s11095-016-1937-x
Zhang M, Wang W, Zhou N et al (2017) Near-infrared light triggered photo-therapy, in combination with chemotherapy using magnetofluorescent carbon quantum dots for effective cancer treating. Carbon 118:752–764. https://doi.org/10.1016/j.carbon.2017.03.085
Zhu S, Zhou N, Hao Z et al (2015) Photoluminescent graphene quantum dots for in vitro and in vivo bioimaging using long wavelength emission. RSC Adv 5:39399–39403
Wang T, Zhu S, Jiang X (2015) Toxicity mechanisms of graphene oxide and nitrogen-doped graphene quantum dots in RBCs revealed by surface-enhanced infrared absorption spectroscopy. Toxicol Res 4:885–894
Simeonidis K, Mourdikoudis S, Kaprara E et al (2016) Inorganic engineered nanoparticles in drinking water treatment: a critical review. Environ Sci Water Res Technol 2:43–70. https://doi.org/10.1039/C5EW00152H
Polavarapu L, Manna M, Xu Q-H (2011) Biocompatible glutathione capped gold clusters as one- and two- photon excitation fluorescence contrast agents for live cells imaging. Nano 3:429–434. https://doi.org/10.1039/C0NR00458H
Guan Z, Polavarapu L, Xu Q-H (2010) Enhanced two-photon emission in coupled metal nanoparticles induced by conjugated polymers. Langmuir 26:18020–18023. https://doi.org/10.1021/la103668k
Becker W (2012) Fluorescence lifetime imaging - techniques and applications. J Microsc 247:119–136. https://doi.org/10.1111/j.1365-2818.2012.03618.x
Bradley SJ, Kroon R, Laufersky G et al (2017) Heterogeneity in the fluorescence of graphene and graphene oxide quantum dots. Microchim Acta. https://doi.org/10.1007/s00604-017-2075-9
Bourassa P, Tajmir-Riahi HA (2015) Folic acid binds DNA and RNA at different locations. Int J Biol Macromol 74:337–342. https://doi.org/10.1016/j.ijbiomac.2014.12.007
Palantavida S, Guz NV, Sokolov I (2013) Functionalized ultrabright fluorescent mesoporous silica nanoparticles. Part Part Syst Charact 30:804–811. https://doi.org/10.1002/ppsc.201300143
Su Y, Zhang M, Zhou N et al (2017) Preparation of fluorescent N,P-doped carbon dots derived from adenosine 5′-monophosphate for use in multicolor bioimaging of adenocarcinomic human alveolar basal epithelial cells. Microchim Acta 184:699–706. https://doi.org/10.1007/s00604-016-2039-5
Xiao Q, Liang Y, Zhu F et al (2017) Microwave-assisted one-pot synthesis of highly luminescent N-doped carbon dots for cellular imaging and multi-ion probing. Microchim Acta 184:2429–2438. https://doi.org/10.1007/s00604-017-2242-z
Cheng R, Peng Y, Ge C et al (2017) A turn-on fluorescent lysine nanoprobe based on the use of the alizarin red aluminum(III) complex conjugated to graphene oxide, and its application to cellular imaging of lysine. Microchim Acta 184:3521–3528. https://doi.org/10.1007/s00604-017-2375-0
Zhu S, Zhang J, Qiao C et al (2011) Strongly green-photoluminescent graphene quantum dots for bioimaging applications. Chem Commun 47:6858–6860. https://doi.org/10.1039/c1cc11122a
Huang Y, Bai C, Cao K et al (2014) Chaos to order: an eco-friendly way to synthesize graphene quantum dots. RSC Adv 4:43160–43165. https://doi.org/10.1039/C4RA06757F
Seyfried TN, Shelton LM (2010) Cancer as a metabolic disease. Nutr Metab 7:7. https://doi.org/10.1186/1743-7075-7-7
Neumann M, Gabel D (2002) Simple method for reduction of autofluorescence in fluorescence microscopy. J Histochem Cytochem 50:437–439. https://doi.org/10.1177/002215540205000315
Shcheslavskiy VI, Neubauer A, Bukowiecki R et al (2016) Combined fluorescence and phosphorescence lifetime imaging. Appl Phys Lett 108:091111. https://doi.org/10.1063/1.4943265
Gerritsen HC, Sanders R, Draaijer A et al (1997) Fluorescence lifetime imaging of oxygen in living cells. J Fluoresc 7:11–15. https://doi.org/10.1007/BF02764572
Acknowledgements
Dr. David M. Brown and Prof. Vicki Stone from Heriot-Watt University for their hospitality and advice for determining the nanotoxicity of graphene oxide quantum dots. We look forward to future collaborations. Thank you to the Royal Society London for funding travels to Edinburgh to visit Heriot-Watt University. Hauke Studier for undertaking the initial analysis using MPM. Ruihua Guo from Beijing Normal University who aided in discussion in the initial stages of the project.
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Goreham, R., Schroeder, K.L., Holmes, A. et al. Demonstration of the lack of cytotoxicity of unmodified and folic acid modified graphene oxide quantum dots, and their application to fluorescence lifetime imaging of HaCaT cells. Microchim Acta 185, 128 (2018). https://doi.org/10.1007/s00604-018-2679-8
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DOI: https://doi.org/10.1007/s00604-018-2679-8