131I-labeled PEG and folic acid co-functionalized graphene quantum dots for tumor-targeted imaging

  • Yunhan Wang
  • Hu Song
  • Guanquan Wang
  • Xia Yang
  • Jing Wang
  • Hongyuan WeiEmail author


In this study, we successfully synthesized polyethylene glycol (PEG) and folic acid (FA) co-functionalized graphene quantum dots (GQDs) to improve the biocompatibility and tumor-targeting ability of GQDs simultaneously, and labeled GQDs–PEG–FA with 131I for biological behavior evaluation. The in vitro properties, biodistribution and SPECT imaging of 131I-GQDs–PEG–FA were investigated. The uptake of 131I-GQDs–PEG–FA at tumor sites can be clearly examined via SPECT imaging, which can ascribe to enhanced permeability and retention effect and active targeting effect of FA to folate receptors. The results indicate that 131I-GQDs–PEG–FA can be used as a radioactive probe for detection of tumor cells overexpressing folate receptor.


Graphene quantum dots Polyethylene glycol Folic acid Active targeting Tumor 131



This work was financially supported by the National Nature Science Foundation of China (NSFC-21471138, NSFC-21401176).

Compliance with ethical standards

Conflict of interest

The authors of the manuscript declare that there is no conflict of interest.


  1. 1.
    Schroeder KL, Goreham RV, Nann T (2016) Graphene quantum dots for theranostics and bioimaging. Pharm Res 33:2337–2357CrossRefGoogle Scholar
  2. 2.
    Zheng XT, Ananthanarayanan A, Luo KQ, Chen P (2015) Glowing graphene quantum dots and carbon dots: properties, syntheses, and biological applications. Small 11:1620–1636CrossRefGoogle Scholar
  3. 3.
    Iannazzo D, Pistone A, Salamo M, Galvagno S, Romeo R, Giofre SV, Branca C, Visalli G, Di Pietro A (2017) Graphene quantum dots for cancer targeted drug delivery. Int J Pharm 518:185–192CrossRefGoogle Scholar
  4. 4.
    Chandra A, Deshpande S, Shinde DB, Pillai VK, Singh N (2014) Mitigating the cytotoxicity of graphene quantum dots and enhancing their applications in bioimaging and drug delivery. ACS Macro Lett 3:1064–1068CrossRefGoogle Scholar
  5. 5.
    Chong Y, Ma Y, Shen H, Tu X, Zhou X, Xu J, Dai J, Fan S, Zhang Z (2014) The in vitro and in vivo toxicity of graphene quantum dots. Biomaterials 35:5041–5048CrossRefGoogle Scholar
  6. 6.
    Abdullah Al N, Lee JE, 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 10:3736–3744CrossRefGoogle Scholar
  7. 7.
    Huang CL, Huang CC, Mai FD, Yen CL, Tzing SH, Hsieh HT, Ling YC, Chang JY (2015) Application of paramagnetic graphene quantum dots as a platform for simultaneous dual-modality bioimaging and tumor-targeted drug delivery. J Mater Chem B 3:651–664CrossRefGoogle Scholar
  8. 8.
    Wang X, Sun X, Lao J, He H, Cheng T, Wang M, Wang S, Huang F (2014) Multifunctional graphene quantum dots for simultaneous targeted cellular imaging and drug delivery. Colloid Surface B 122:638–644CrossRefGoogle Scholar
  9. 9.
    Zou F, Zhou H, Tan TV, Kim J, Koh K, Lee J (2015) Dual-mode SERS-fluorescence immunoassay using graphene quantum dot labeling on one-dimensional aligned magnetoplasmonic nanoparticles. ACS Appl Mater Int 7:12168–12175CrossRefGoogle Scholar
  10. 10.
    Zheng XT, He HL, Li CM (2013) Multifunctional graphene quantum dots-conjugated titanate nanoflowers for fluorescence-trackable targeted drug delivery. RSC Adv 3:24853–24857CrossRefGoogle Scholar
  11. 11.
    Song H, Wang YH, Wang J, Wang GQ, He JH, Wei HY, Luo SZ (2018) Prepartion and biodistribution of 131I-labeled graphene quantum dots. J Radioanal Nucl Chem 316:685–690CrossRefGoogle Scholar
  12. 12.
    Guo W, Lee RJ (1999) Receptor-targeted gene delivery viafolate-conjugated polyethylenimine. AAPS Pharmsci 1:20–26CrossRefGoogle Scholar
  13. 13.
    Song H, Luo SZ, Wei HY, Song HT, Yang YQ, Zhao WW (2010) In vivo biological behavior of 99mTc(CO)3 labeled fullerol. J Radioanal Nucl Chem 285:635–639CrossRefGoogle Scholar
  14. 14.
    Maeda H (2012) Macromolecular therapeutics in cancer treatment: the EPR effect and beyond. J Control Rel 164:138–144CrossRefGoogle Scholar
  15. 15.
    Maeda H, Matsumura Y (2011) EPR effect based drug design and clinical outlook for enhanced cancer chemotherapy. Adv Drug Deliv Rev 63:129–130CrossRefGoogle Scholar
  16. 16.
    Maeda H, Nakamura H, Fang J (2013) The EPR effect for macromolecular drug delivery to solid tumors: improvement of tumor uptake, lowering of systemic toxicity, and distinct tumor imaging in vivo. Adv Drug Deliv Rev 65:71–79CrossRefGoogle Scholar
  17. 17.
    Zhang RY, Wang ZY, Yang XQ, Xuan Y, Cheng K, Li C, Song XL, An J, Hou XL, Zhao YD (2017) Folic acid modified Pluronic F127 coating Ag2S quantum dot for photoacoustic imaging of tumor cell-targeting. Nanotechnology. 29:055101CrossRefGoogle Scholar
  18. 18.
    Tian Y, Li JC, Zhu JX, Zhu N, Zhang HM, Liang L, Sun L (2017) Folic acid-targeted etoposide cubosomes for theranostic application of cancer cell imaging and therapy. Med Sci Monit 23:2426–2435CrossRefGoogle Scholar
  19. 19.
    Hai X, Wang YT, Hao XY, Chen XW, Wang JH (2018) Folic acid encapsulated graphene quantum dots for ratiometric pH sensing and specific multicolor imaging in living cells. Sens Actuat B Chem 268:61–69CrossRefGoogle Scholar
  20. 20.
    Lin JY, Hu WW, Gao FL, Qin JB, Cheng P, Lu XW (2018) Folic acid-modified diatrizoic acid-linked dendrimer-entrapped gold nanoparticles enable targeted CT imaging of human cervical cancer. J Cancer 9:564–577CrossRefGoogle Scholar

Copyright information

© Akadémiai Kiadó, Budapest, Hungary 2019

Authors and Affiliations

  1. 1.Department of Nuclear MedicineFirst Affiliated Hospital of Southwest Medical UniversityLuzhouPeople’s Republic of China
  2. 2.Institute of Nuclear Physics and ChemistryChina Academy of Engineering PhysicsMianyangPeople’s Republic of China

Personalised recommendations