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Microchimica Acta

, 186:231 | Cite as

Functionalized fluorescent carbon nanostructures for targeted imaging of cancer cells: a review

  • Meghdad Pirsaheb
  • Somayeh MohammadiEmail author
  • Abdollah Salimi
  • Mehrdad Payandeh
Review Article
  • 109 Downloads

Abstract

This short review (with 72 refs.) summarizes the state of the art in fluorometric methods for targeted imaging of cancer cells and tumor tissues in order to differentiate between normal cells and cancer cells. Following an introduction into the field and after presenting an overview on the most commonly used carbon dots and graphene quantum dots, we describe methods based on peptide based targeting, aptamer based targeting, antibody based targeting, and ligand-based targeting. A concluding section summarizes the current state and challenges, and discusses future perspectives.

Graphical abstract

An overview is given on the applications of carbon dots (CDs) in target-specific imaging and differentiation of cancerous cells from normal cells. Several classes of ligands (including aptamers, peptides, antibodies), especially small molecules (such as FA)) have been reported for functionalizing of CDs.

Keywords

Carbon based materials Covalent and non-covalent modification Heteroatom doping Polymer passivation Folate receptors Cell imaging Cancer cells 

Notes

Acknowledgments

The authors gratefully acknowledge the Research Council of Kermanshah University of Medical Sciences (Grant Number: 96386) for the financial support.

Compliance with ethical standards

The author(s) declare that they have no competing interests.

References

  1. 1.
    Bajaj A, Miranda OR, Kim IB, Phillips RL, Jerry DJ, Bunz UH, Rotello VM (2009) Detection and differentiation of normal, cancerous, and metastatic cells using nanoparticle-polymer sensor arrays. Proc Natl Acad Sci 106(27):10912–10916CrossRefGoogle Scholar
  2. 2.
    Pedram P, Mahani M, Torkzadeh-Mahani M, Hasani Z, Ju H (2016) Cadmium sulfide quantum dots modified with the human transferrin protein siderophiline for targeted imaging of breast cancer cells. Microchim Acta 183(1):67–71CrossRefGoogle Scholar
  3. 3.
    Ge X, Sun L, Dang S, Liu J, Xu Y, Wei Z, Shi L, Zhang H (2015) Mesoporous upconversion nanoparticles modified with a Tb (III) complex to display both green upconversion and downconversion luminescence for in vitro bioimaging and sensing of temperature. Microchim Acta 182(9–10):1653–1660CrossRefGoogle Scholar
  4. 4.
    Mazrad ZAI, Choi CA, Kim SH, Lee G, Lee S, In I, Lee KD, Park SY (2017) Target-specific induced hyaluronic acid decorated silica fluorescent nanoparticles@ polyaniline for bio-imaging guided near-infrared photothermal therapy. J Mater Chem B 5(34):7099–7108CrossRefGoogle Scholar
  5. 5.
    Kumar SSD, Mahesh A, Antoniraj MG, Rathore HS, Houreld NN, Kandasamy R (2018) Cellular imaging and folate receptor targeting delivery of gum kondagogu capped gold nanoparticles in cancer cells. Int J Biol Macromol 109:220–230CrossRefGoogle Scholar
  6. 6.
    Wang J, Zhang G, Li Q, Jiang H, Liu C, Amatore C, Wang X (2013) In vivo self-bio-imaging of tumors through in situ biosynthesized fluorescent gold nanoclusters. Sci Rep 3:1157CrossRefGoogle Scholar
  7. 7.
    Xia JM, Wei X, Chen XW, Shu Y, Wang JH (2018) Folic acid modified copper nanoclusters for fluorescent imaging of cancer cells with over-expressed folate receptor. Microchim Acta 185(3):205CrossRefGoogle Scholar
  8. 8.
    Alkahtani MH, Alghannam F, Jiang L, Almethen A, Rampersaud AA, Brick R, Gomes CL, Scully MO, Hemmer PR (2018) Fluorescent nanodiamonds: past, present, and future. Nanophotonics 7(8):1423–1453CrossRefGoogle Scholar
  9. 9.
    Roy P, Chen PC, Periasamy AP, Chen YN, Chang HT (2015) Photoluminescent carbon nanodots: synthesis, physicochemical properties and analytical applications. Mater Today 18(8):447–458CrossRefGoogle Scholar
  10. 10.
    Xia J, Zhuang YT, Yu YL, Wang JH (2017) Highly fluorescent carbon polymer dots prepared at room temperature, and their application as a fluorescent probe for determination and intracellular imaging of ferric ion. Microchim Acta 184(4):1109–1116CrossRefGoogle Scholar
  11. 11.
    Su Y, Zhang M, Zhou N, Shao M, Chi C, Yuan P, Zhao C (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(3):699–706CrossRefGoogle Scholar
  12. 12.
    Cayuela A, Soriano ML, Carrillo-Carrión C, Valcárcel M (2016) Semiconductor and carbon-based fluorescent nanodots: the need for consistency. Chem Commun 52:1311–1326CrossRefGoogle Scholar
  13. 13.
    Xu X, Ray R, Gu Y, Ploehn HJ, Gearheart L, Raker K, Scrivens WA (2004) Electrophoretic analysis and purification of fluorescent single-walled carbon nanotube fragments. J Am Chem Soc 126(40):12736–12737CrossRefGoogle Scholar
  14. 14.
    Miao P, Han K, Tang Y, Wang B, Lin T, Cheng W (2015) Recent advances in carbon nanodots: synthesis, properties and biomedical applications. Nanoscale 7(5):1586–1595CrossRefGoogle Scholar
  15. 15.
    Zhi B, Cui Y, Wang S, Frank BP, Williams DN, Brown RP, Melby ES, Hamers RJ, Rosenzweig Z, Fairbrother DH, Orr G, Haynes CL (2018) Malic Acid Carbon Dots: From Super-resolution Live-Cell Imaging to Highly Efficient Separation. ACS Nano 12(6):5741–5752CrossRefGoogle Scholar
  16. 16.
    Pelaz B et al (2017) Diverse Applications of Nanomedicine. ACS Nano 11(3):2313–2381CrossRefGoogle Scholar
  17. 17.
    Goreham RV, Schroeder KL, Holmes A, Bradley SJ, Nann T (2018) 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(2):128CrossRefGoogle Scholar
  18. 18.
    Zhou J, Zhou H, Tang J, Deng S, Yan F, Li W, Qu M (2017) Carbon dots doped with heteroatoms for fluorescent bioimaging: a review. Microchim Acta 184(2):343–368CrossRefGoogle Scholar
  19. 19.
    Zhu S, Song Y, Zhao X, Shao J, Zhang J, Yang B (2015) The photoluminescence mechanism in carbon dots (graphene quantum dots, carbon nanodots, and polymer dots): current state and future perspective. Nano research 8(2):355–381CrossRefGoogle Scholar
  20. 20.
    Li Y, Zhang N, Zhao WW, Jiang DC, Xu JJ, Chen HY (2017) Polymer dots for photoelectrochemical bioanalysis. Anal chem 89(9):4945–4950CrossRefGoogle Scholar
  21. 21.
    Georgakilas V, Perman JA, Tucek J, Zboril R (2015) Broad family of carbon nanoallotropes: classification, chemistry, and applications of fullerenes, carbon dots, nanotubes, graphene, nanodiamonds, and combined superstructures. Chem rev 115(11):4744–4822CrossRefGoogle Scholar
  22. 22.
    Paulo S, Palomares E, Martinez-Ferrero E (2016) Graphene and carbon quantum dot-based materials in photovoltaic devices: From synthesis to applications. Nanomaterials 6(9):157CrossRefGoogle Scholar
  23. 23.
    Yan F, Jiang Y, Sun X, Bai Z, Zhang Y, Zhou X (2018) Surface modification and chemical functionalization of carbon dots: a review. Microchim Acta 185(9):424CrossRefGoogle Scholar
  24. 24.
    Yang Y, Wang X, Liao G, Liu X, Chen Q, Li H, Lu L, Zhao P, Yu Z (2018) iRGD-decorated red shift emissive carbon nanodots for tumor targeting fluorescence imaging. J Colloid Interface Sci 509:515–521CrossRefGoogle Scholar
  25. 25.
    Li Q, Ohulchanskyy TY, Liu R, Koynov K, Wu D, Best A, Kumar R, Bonoiu A, Prasad PN (2010) Photoluminescent Carbon Dots as Biocompatible Nanoprobes for Targeting Cancer Cells in Vitro. J Phys Chem C 114:12062–12068CrossRefGoogle Scholar
  26. 26.
    Lee CH, Rajendran R, Jeong M-S, Ko HY, Joo JY, Cho S, Chang YW, Kim S (2013) Bioimaging of targeting cancers using aptamer-conjugated carbon nanodots. Chem Commun 49:6543–6545CrossRefGoogle Scholar
  27. 27.
    Motaghi H, Ayatollahi Mehrgardi M, Bouvet P (2017) Carbon Dots-AS1411 Aptamer Nanoconjugate for Ultrasensitive Spectrofluorometric Detection of Cancer Cells. Sci Rep 7:10513CrossRefGoogle Scholar
  28. 28.
    Su H, Liao Y, Wu F, Sun X, Liu H, Wang K, Zhu X (2018) Cetuximab-conjugated iodine doped carbon dots as a dual fluorescent/CT probe for targeted imaging of lung cancer cells. Colloids Surf B 170:194–200CrossRefGoogle Scholar
  29. 29.
    Wang J, Liu J (2016) PEI-Folic acid modified carbon nanodots for cancer cell targeted delivery and two-photon excitation imaging. RSC Adv 6:19662–19668CrossRefGoogle Scholar
  30. 30.
    Wang Ch XZ, Lin H, Huang Y, Zhang C (2015) Large Scale Synthesis of Highly Stable Fluorescent Carbon Dots Using Silica Spheres as Carriers for Targeted Bioimaging of Cancer Cells. Part Part Syst Charact 32:944–951CrossRefGoogle Scholar
  31. 31.
    Chiu S-H, Gedda G, Girma WM, Chen J-K, Ling Y-C, Ghule AV, Ou K-L, Chang J-Y (2016) Rapid fabrication of carbon quantum dots as multifunctional nanovehicles for dual-modal targeted imaging and chemotherapy. Acta Biomaterialia 46:151–164CrossRefGoogle Scholar
  32. 32.
    Das RK, Mohapatra S (2017) Highly luminescent, heteroatom-doped carbon quantum dots for ultrasensitive sensing of glucosamine and targeted imaging of liver cancer cells. J Mater Chem B 5:2190–2197CrossRefGoogle Scholar
  33. 33.
    Hamd-Ghadareh S, Salimi A, Fathi F, Bahrami S (2017) An amplified comparative fluorescence resonance energy transfer immunosensing of CA125 tumor marker and ovarian cancer cells using green and economic carbon dots for bio-applications in labeling, imaging and sensing. Biosens Bioelectron 96:308–316CrossRefGoogle Scholar
  34. 34.
    Hamd-Ghadareh S, Salimi A, Parsa S, Fathi F Simultaneous biosensing of CA125 and CA15–3 tumor markers and imaging of OVCAR-3 and MCF-7 cells lines via bi-color FRET phenomenon using dual blue-green luminescent carbon dots with single excitation wavelength. Int J Biol Macromol 118:617–628Google Scholar
  35. 35.
    Han C, Xu H, Wang R, Wang K, Dai Y, Liu Q, Guo M, Li J, Xu K (2016) Synthesis of a multifunctional manganese(II)– carbon dots hybrid and its application as an efficient magnetic-fluorescent imaging probe for ovarian cancer cell imaging. J Mater Chem B 4:5798–5802CrossRefGoogle Scholar
  36. 36.
    Zhang M, Fang Z, Zhao X, Niu Y, Lou J, Zhao L, Wu Y, Zou S, Du F, Shao Q (2016) Hyaluronic acid functionalized nitrogen-doped carbon quantum dots for targeted specific bioimaging. RSC Adv 6:104979–104984CrossRefGoogle Scholar
  37. 37.
    Gao N, Yang W, Nie H, Gong Y, Jing J, Gao L, Zhang X (2017) Turn-on theranostic fluorescent nanoprobe by electrostatic self-assembly of carbon dots with doxorubicin for targeted cancer cell imaging, in vivo hyaluronidase analysis, and targeted drug delivery. Biosens Bioelectron 96:300–307CrossRefGoogle Scholar
  38. 38.
    Lei D, Yang W, Gong Y, Jing J, Nie H, Yu B, Zhang X (2016) Non-covalent decoration of carbon dots with folic acid via a polymer-assisted strategy for fast and targeted cancer cell fluorescence imaging. Sens Actuators B Chem 230:714–720CrossRefGoogle Scholar
  39. 39.
    Zhang M, Zhao X, Fang Z, Niu Y, Lou J, Wu Y, Zou S, Xia S, Sun M, Du F (2017) Fabrication of HA/PEI-functionalized carbon dots for tumor targeting, intracellular imaging and gene delivery. RSC Adv 7:3369–3375CrossRefGoogle Scholar
  40. 40.
    Liu Q, Xu S, Niu C, Li M, He D, Lu Z, Ma L, Na N, Huang F, Jiang H, Ouyang J (2015) Distinguish cancer cells based on targeting turn-on fluorescence imaging by folate functionalized green emitting carbon dots. Biosens Bioelectron 64:119–125CrossRefGoogle Scholar
  41. 41.
    Song Y, Shi W, Chen W, Li X, Ma H (2012) Fluorescent carbon nanodots conjugated with folic acid for distinguishing folate-receptor-positive cancer cells from normal cells. J Mater Chem 22:12568–12573CrossRefGoogle Scholar
  42. 42.
    Qiao L, Sun T, Zheng X, Zheng M, Xie Z (2018) Exploring the optimal ratio of D-glucose/L-aspartic acid for targeting carbon dots toward brain tumor cells. Mater Sci Eng C 85:1–6CrossRefGoogle Scholar
  43. 43.
    Zheng M, Ruan S, Liu S, Sun T, Qu D, Zhao H, Xie Z, Gao H, Jing X, Sun Z (2015) Self-Targeting Fluorescent Carbon Dots for Diagnosis of Brain Cancer Cells. ACS Nano 9(11):11455–11461CrossRefGoogle Scholar
  44. 44.
    Aiyer S, Prasad R, Kumar M, Nirvikar K, Jain B, Kushwaha OS (2016) Fluorescent carbon nanodots for targeted in vitro cancer cell imaging. Applied Mater Today 4:71–77CrossRefGoogle Scholar
  45. 45.
    Zhao X, Zhang J, Shi L, Xian M, Dong C, Shuang S (2017) Folic acid-conjugated carbon dots as green fluorescent probes based on cellular targeting imaging for recognizing cancer cells. RSC Adv 7:42159–42167CrossRefGoogle Scholar
  46. 46.
    Qian J, Quan F, Zhao F, Wu C, Wang Z, Zhou L (2018) Aconitic acid derived carbon dots: Conjugated interaction for the detection of folic acid and fluorescence targeted imaging of folate receptor overexpressed cancer cells. Sens Actuators B Chem 262:444–451CrossRefGoogle Scholar
  47. 47.
    Zhang J, Zhao X, Xian M, Dong C, Shuang S (2018) Folic acid-conjugated green luminescent carbon dots as a nanoprobe for identifying folate receptor-positive cancer cells. Talanta 183:39–47CrossRefGoogle Scholar
  48. 48.
    Choi Y, Kim S, Choi M-H, Ryoo S-R, Park J, Min D-H, Kim B-S (2014) Highly Biocompatible Carbon Nanodots for Simultaneous Bioimaging and Targeted Photodynamic Therapy In Vitro and In Vivo. Adv Funct Mater 24:5781–5789CrossRefGoogle Scholar
  49. 49.
    Bhunia SK, Maity AR, Nandi S, Stepensky D, Jelinek R (2016) Imaging Cancer Cells Expressing the Folate Receptor with Carbon Dots Produced from Folic Acid. Chem Bio Chem 17:614–619CrossRefGoogle Scholar
  50. 50.
    Yang X, Yang X, Li Z, Li S, Han Y, Chen Y, Bu X, Su Ch XH, Jiang Y, Lin Q (2015) Photoluminescent carbon dots synthesized by microwave treatment for selective image of cancer cells. J Colloid Interface Sci 456:1–6CrossRefGoogle Scholar
  51. 51.
    Liu H, Li Z, Sun Y, Geng X, Hu Y, Meng H, Ge J, Qu L (2018) Synthesis of Luminescent Carbon Dots with Ultrahigh Quantum Yield and Inherent Folate Receptor Positive Cancer Cell Targetability. Sci Rep 8:1086–1093CrossRefGoogle Scholar
  52. 52.
    Yang X, Wang Y, Shen X, Su C, Yang J, Piao M, Jia F, Gao G, Zhang L, Lin Q (2017) One-step synthesis of photoluminescent carbon dots with excitation in dependent emission for selective bioimaging and gene delivery. J Colloid Interface Sci 492:1–7CrossRefGoogle Scholar
  53. 53.
    Demir B, Lemberger MM, Panagiotopoulou M, Medina Rangel PX, Timur S, Hirsch T, Tse Sum Bui B, Wegener J, Haupt K (2018) Tracking Hyaluronan: Molecularly Imprinted Polymer Coated Carbon Dots for Cancer Cell Targeting and Imaging. ACS Appl Mater Interfaces 10(4):3305–3313CrossRefGoogle Scholar
  54. 54.
    Liu Q, Guo B, Rao Z, Zhang B, Gong JR (2013) Strong Two-Photon-Induced Fluorescence from Photostable, Biocompatible Nitrogen-Doped Graphene Quantum Dots for Cellular and Deep-Tissue Imaging. Nano Lett 13:2436–2441CrossRefGoogle Scholar
  55. 55.
    Nigam P, Waghmode S, Louis M, Wangnoo S, Chavan P, Sarkar D (2014) Graphene quantum dots conjugated albumin nanoparticles for targeted drug delivery and imaging of pancreatic cancer. J. Mater. Chem. B 2:3190–3195CrossRefGoogle Scholar
  56. 56.
    Huang C-L, Huang C-C, Mai F-D, Yen C-L, Tzing S-H, Hsieh H-T, Ling Y-C, Chang J-Y (2015) Application of paramagnetic graphene quantum dots as a platform for simultaneous dual-modality bioimaging and tumor targeted drug delivery. J Mater Chem B. 3(4):651–664CrossRefGoogle Scholar
  57. 57.
    Su Z, Shen H, Wang H, Wang J, Li J, Nienhaus GU, Shang L, Wei G (2015) Motif-Designed Peptide Nanofibers Decorated with Graphene Quantum Dots for Simultaneous Targeting and Imaging of Tumor Cells. Adv Funct Mater 25:5472–5478CrossRefGoogle Scholar
  58. 58.
    Wang X, Sun X, He H, Yang H, Lao J, Song Y, Xia Y, Xu H, Zhang X, Huang F (2015) A two-component active targeting theranostic agent based on graphene quantum dots. J Mater Chem B 3:3583–3590CrossRefGoogle Scholar
  59. 59.
    Abdullah-Al-Nahain LJ-E, In I, Lee H, Lee KD, Jeong JH, Park SY (2013) Target delivery and cell imaging using hyaluronic acid functionalized graphene quantum dots. Mol Pharm. 10(10):3736–3744CrossRefGoogle Scholar
  60. 60.
    Ostadhossein F, Pan D (2017) Functional carbon nanodots for multiscale imaging and therapy. Wiley Interdiscip Rev Nanomed Nanobiotechnol 9(3):e1436CrossRefGoogle Scholar
  61. 61.
    Li J, Jiao Y, Feng L, Zhong Y, Zuo G, Xie A, Dong W (2017) Highly N, P-doped carbon dots: rational design, photoluminescence and cellular imaging. Microchim Acta 184(8):2933–2940CrossRefGoogle Scholar
  62. 62.
    Pan L, Sun S, Zhang A, Jiang K, Zhang L, Dong C, Huang Q, Wu A, Lin H (2015) Truly Fluorescent Excitation-Dependent Carbon Dots and Their Applications in Multicolor Cellular Imaging and Multidimensional Sensing. Adv mater 27(47):7782–7787CrossRefGoogle Scholar
  63. 63.
    Liu C, Wang R, Wang B, Deng Z, Jin Y, Kang Y, Chen J (2018) Orange, yellow and blue luminescent carbon dots controlled by surface state for multicolor cellular imaging, light emission and illumination. Microchim Acta 185(12):539CrossRefGoogle Scholar
  64. 64.
    Wang EC, Wang AZ (2014) Nanoparticles and their applications in cell and molecular biology. Integr Biol (Camb) 6(1):9–26CrossRefGoogle Scholar
  65. 65.
    Xu Q, Kuang T, Liu Y, Cai L, Peng X, Sreeprasad Th S, Zhao P, Yu Z, Li N (2016) Heteroatom-doped carbon dots: synthesis, characterization, properties, photoluminescence mechanism and biological applications. J. Mater. Chem. B 4:7204–7219CrossRefGoogle Scholar
  66. 66.
    Xiao Q, Liang Y, Zhu F, Lu S, Huang S (2017) Microwave-assisted one-pot synthesis of highly luminescent N-doped carbon dots for cellular imaging and multi-ion probing. Microchim Acta 184(7):2429–2438CrossRefGoogle Scholar
  67. 67.
    Zuo P, Lu X, Sun Z, Guo Y, He H (2016) A review on syntheses, properties, characterization and bioanalytical applications of fluorescent carbon dots. Microchim Acta 183:519–542CrossRefGoogle Scholar
  68. 68.
    Liu W, Li C, Ren Y, Sun X, Pan W, Li Y, Wang J, Wang W (2016) Carbon dots: surface engineering and applications. J. Mater. Chem. B 4:5772–5788CrossRefGoogle Scholar
  69. 69.
    Han B, Wang W, Wu H, Fang F, Wang N, Zhang X, Xu S (2012) Polyethyleneimine modified fluorescent carbon dots and their application in cell labeling. Colloids Surf B: Biointerfaces 100:209–214CrossRefGoogle Scholar
  70. 70.
    Gui W, Zhang J, Chen X, Yu D, Ma Q (2018) N-Doped graphene quantum dot@ mesoporous silica nanoparticles modified with hyaluronic acid for fluorescent imaging of tumor cells and drug delivery. Microchim Acta 185(1):66CrossRefGoogle Scholar
  71. 71.
    Wang HJ, Zhang J, Liu YH, Luo TY, He X, Yu XQ (2017) Hyaluronic acid-based carbon dots for efficient gene delivery and cell imaging. RSC Advances 7(25):15613–15624CrossRefGoogle Scholar
  72. 72.
    Chen H, Shi D, Wang Y, Zhang L, Zhang Q, Wang B, Xia C (2015) The advances in applying inorganic fluorescent nanomaterials for the detection of hepatocellular carcinoma and other cancers. Rsc Advances. 5(97):79572–79584CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Research Center for Environmental Determinants of Health (RCEDH)Kermanshah University of Medical SciencesKermanshahIran
  2. 2.Department of ChemistryUniversity of KurdistanSanandajIran
  3. 3.Research Center for NanotechnologyUniversity of KurdistanSanandajIran
  4. 4.Regenerative Medicine Research CenterKermanshah University of Medical SciencesKermanshahIran

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