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Graphene Oxide - Gelatin Nanohybrids as Functional Tools for Enhanced Carboplatin Activity in Neuroblastoma Cells

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Abstract

Purpose

Preparation of Nanographene oxide (NGO) - Gelatin hybrids for efficient treatment of Neuroblastoma.

Methods

Nanohybrids were prepared via non-covalent interactions. Spectroscopic tools have been used to discriminate the chemical states of NGO prior and after gelatin coating, with UV visible spectroscopy revealing the maximum binding capacity of gelatin to NGO. Raman and X-ray photoelectron spectroscopy (XPS) demonstrated NGO and Gelatin_NGO nanohybrids through a new chemical environments produced after noncovalent interaction. Microscopic analyses, atomic force microscopy (AFM) and scanning electron microscopy (SEM) are used to estimate the thickness of samples and the lateral width in the nanoscale, respectively.

Results

The cell viability assay validated Gelatin_NGO nanohybrids as a useful nanocarrier for Carboplatin (CP) release and delivery, without obvious signs of toxicity. The nano-sized NGO (200 nm and 300 nm) did not enable CP to kill the cancer cells efficiently, whilst the CP loaded Gel_NGO 100 nm resulted in a synergistic activity through increasing the local concentration of CP inside the cancer cells.

Conclusions

The nanohybrids provoked high stability and dispersibility in physiological media, as well as enhanced the anticancer activity of the chemotherapy agent Carboplatin (CP) in human neuroblastoma cells.

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Abbreviations

AFM:

Atomic force microscopy

CP:

Carboplatin

CP@Gel:

Gelatin loaded with carboplatin

CP@Gel_NGO:

Gelatin coated Nanographene oxide loaded with Carboplatin

CP@NGO:

Nanographene oxide loaded with Carboplatin

CPT:

Camptothecin

DMEM:

Dulbecco’s modified eagle medium

DOX:

Doxorubicin

EDAX:

Energy dispersive X-ray analysis

FBS:

Fetal bovine serum

FWHM:

Full width at half maximum

Gel:

Gelatin

Gel_NGO:

Gelatin coated nanographene oxide

GNS:

Graphene nanosheets

GO:

Graphene oxide

hMSCs:

Human mesenchymal stem cells

IMR-32:

Human neuroblastoma cells

LE:

Loading efficiency

NGO:

Nanographene oxide

PAMAM:

Polyamidoamide

PBS:

Phosphate buffered saline

PEG:

Polyethylene glycol

Rho:

Rhodamine B

Rho@Gel_NGO:

Gelatin coated nanographene oxide loaded with rhodamine B

RT:

Room temperature

SD:

Standard deviation

SEM:

Scanning electron microscope

SN-38:

7-ethyl-10-hydroxycamptothecin

XPS:

X-ray photoelectron spectroscopy

References

  1. Novoselov KS, Jiang D, Schedin F, Booth TJ, Khotkevich VV, Morozov SV, et al. Two-dimensional atomic crystals. Proc Natl Acad Sci U S A. 2005;102:10451–3.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Novoselov KS, Geim AK, Morozov SV, Jiang D, Zhang Y, Dubonos SV, et al. Electric field effect in atomically thin carbon films. Science. 2004;306:666–9.

    Article  CAS  PubMed  Google Scholar 

  3. Makharza S, Cirillo G, Bachmatiuk A, Ibrahim I, Ioannides N, Trzebicka B, et al. Graphene oxide-based drug delivery vehicles: functionalization, characterization, and cytotoxicity evaluation. J Nanoparticle Res. 2013;15:2099–124.

    Article  Google Scholar 

  4. Georgakilas V, Otyepka M, Bourlinos AB, Chandra V, Kim N, Kemp KC, et al. Functionalization of graphene: covalent and non-covalent approaches, derivatives and applications. Chem Rev. 2012;112:6156–214.

    Article  CAS  PubMed  Google Scholar 

  5. Wang Y, Li Z, Wang J, Li J, Lin Y. Graphene and graphene oxide: biofunctionalization and applications in biotechnology. Trends Biotechnol. 2011;29:205–12.

    Article  PubMed  Google Scholar 

  6. Zhang W, Guo Z, Huang D, Liu Z, Guo X, Zhong H. Synergistic effect of chemo-photothermal therapy using PEGylated graphene oxide. Biomaterials. 2011;32:8555–61.

    Article  CAS  PubMed  Google Scholar 

  7. Liu Z, Robinson JT, Sun X, Dai H. PEGylated nano-graphene oxide for delivery of water insoluble cancer drugs. J Am Chem Soc. 2008;130:10876–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Shen H, Liu M, He H, Zhang L, Huang J, Chong Y, et al. PEGylated graphene oxide-mediated protein delivery for cell function regulation. ACS Appl Mater Interfaces. 2012;4:6317–23.

    Article  CAS  PubMed  Google Scholar 

  9. Tan X, Feng L, Zhang J, Yang K, Zhang S, Liu Z, et al. Functionalization of graphene oxide generates a unique interface for selective serum protein interactions. ACS Appl Mater Interfaces. 2013;5:1370–7.

    Article  CAS  PubMed  Google Scholar 

  10. Yang K, Zhang S, Zhang G, Sun X, Lee S-T, Liu Z. Graphene in mice: ultrahigh in vivo tumor uptake and efficient photothermal therapy. Nano Lett. 2010;10:3318–23.

    Article  CAS  PubMed  Google Scholar 

  11. Lee DY, Khatun Z, Lee J-H, Lee Y-K, In I. Blood compatible graphene/heparin conjugate through noncovalent chemistry. Biomacromolecules. 2011;12:336–41.

    Article  CAS  PubMed  Google Scholar 

  12. Zhang S, Yang K, Feng L, Liu Z. In vitro and in vivo behaviors of dextran functionalized graphene. Carbon. 2011;49:4040–9.

    Article  CAS  Google Scholar 

  13. Tang L, Wang Y, Liu Y, Li J. DNA-directed self-assembly of graphene oxide with applications to ultrasensitive oligonucleotide assay. 2011;3817–22.

  14. Bao H, Pan Y, Ping Y, Sahoo NG, Wu T, Li L, et al. Chitosan-functionalized graphene oxide as a nanocarrier for drug and gene delivery. Small. 2011;7:1569–78.

    Article  CAS  PubMed  Google Scholar 

  15. An J, Gou Y, Yang C, Hu F, Wang C. Synthesis of a biocompatible gelatin functionalized graphene nanosheets and its application for drug delivery. Mater Sci Eng C. 2013;33:2827–37.

    Article  CAS  Google Scholar 

  16. Makharza S, Cirillo G, Bachmatiuk A, Vittorio O, Mendes RG, Oswald S, et al. Size-dependent nanographene oxide as a platform for efficient carboplatin release. J Mater Chem B. 2013;1:6107–14.

    Article  CAS  Google Scholar 

  17. Cirillo G, Vittorio O, Hampel S, Spizzirri UG, Picci N, Iemma F. Incorporation of carbon nanotubes into a gelatin-catechin conjugate: innovative approach for the preparation of anticancer materials. Int J Pharm. 2013;446:176–82.

    Article  CAS  PubMed  Google Scholar 

  18. Zheng W, Zheng YF. Gelatin-functionalized carbon nanotubes for the bioelectrochemistry of hemoglobin. Electrochem Commun. 2007;9:1619–23.

    Article  CAS  Google Scholar 

  19. Liu K, Zhang JJ, Cheng FF, Zheng TT, Wang C, Zhu JJ. Green and facile synthesis of highly biocompatible graphene nanosheets and its application for cellular imaging and drug delivery. J Mater Chem. 2011;21:12034–40.

    Article  CAS  Google Scholar 

  20. Hummers WS, Offeman RE. Preparation of graphitic oxide. J Am Chem Soc. 1958;80:1339–9.

  21. Sun X, Luo D, Liu J, Evans DG. Monodisperse chemically modified graphene obtained by density gradient ultracentrifugal rate separation. ACS Nano. 2010;4:3381–9.

    Article  CAS  PubMed  Google Scholar 

  22. Horcas I, Fernández R, Gómez-Rodríguez JM, Colchero J, Gómez-Herrero J, Baro AM. WSXM: a software for scanning probe microscopy and a tool for nanotechnology. Rev Sci Instrum. 2007;78:013705–8.

    Article  CAS  PubMed  Google Scholar 

  23. Schniepp HC, Li JL, McAllister MJ, Sai H, Herrera-Alonso M, Adamson DH, et al. Functionalized single graphene sheets derived from splitting graphite oxide. J Phys Chem B. 2006;110:8535–9.

    Article  CAS  PubMed  Google Scholar 

  24. Kudin KN, Ozbas B, Schniepp HC, Prud’homme RK, Aksay IA, Car R. Raman spectra of graphite oxide and functionalized graphene sheets. Nano Lett. 2008;8:36–41.

    Article  CAS  PubMed  Google Scholar 

  25. Pimenta MA, Dresselhaus G, Dresselhaus MS, Cançado LG, Jorio A, Saito R. Studying disorder in graphite-based systems by Raman spectroscopy. Phys Chem Chem Phys. 2007;9:1276–91.

    Article  CAS  PubMed  Google Scholar 

  26. Haubner K, Murawski J, Olk P. The route to functional graphene oxide. ChemPhysChem. 2010;11:2131–9.

    Article  CAS  PubMed  Google Scholar 

  27. Yang H, Shan C, Li F, Han D, Zhang Q, Niu L. Covalent functionalization of polydisperse chemically-converted graphene sheets with amine-terminated ionic liquid. Chem. Commun. 2009;3880–2.

  28. Biesinger MC, Payne BP, Grosvenor AP, Lau LWM, Gerson AR, Smart RSC. Resolving surface chemical states in XPS analysis of first row transition metals, oxides and hydroxides: Cr, Mn, Fe, Co and Ni. Appl Surf Sci. 2011;257:2717–30.

    Article  CAS  Google Scholar 

  29. Yi H-B, Lee HM, Kim KS. Interaction of benzene with transition metal cations: theoretical study of structures, energies, and IR spectra. J Chem Theory Comput. 2009;5:1709–17.

    Article  CAS  Google Scholar 

  30. Spizzirri UG, Hampel S, Cirillo G, Nicoletta FP, Hassan A, Vittorio O, et al. Spherical gelatin/CNTs hybrid microgels as electro-responsive drug delivery systems. Int J Pharm. 2013;448:115–22.

    Article  CAS  PubMed  Google Scholar 

  31. Yue H, Wei W, Yue Z, Wang B, Luo N, Gao Y, et al. The role of the lateral dimension of graphene oxide in the regulation of cellular responses. Biomaterials. 2012;33:4013–21.

    Article  CAS  PubMed  Google Scholar 

  32. Vittorio O, Cirillo G, Iemma F, Di Turi G, Jacchetti E, Curcio M, et al. Dextran-catechin conjugate: a potential treatment against the pancreatic ductal adenocarcinoma. Pharm Res. 2012;29:2601–14.

    Article  CAS  PubMed  Google Scholar 

  33. Akhavan O, Ghaderi E, Akhavan A. Size-dependent genotoxicity of graphene nanoplatelets in human stem cells. Biomaterials. 2012;33:8017–25.

    Article  CAS  PubMed  Google Scholar 

  34. Chng ELK, Sofer Z, Pumera M. Cytotoxicity profile of highly hydrogenated graphene. Chem Eur J. 2014;20:6366–73.

    Article  CAS  PubMed  Google Scholar 

  35. Ku SH, Lee M, Park CB. Carbon-based nanomaterials for tissue engineering. Adv Healthcare Mat. 2013;2:244–60.

    Article  CAS  Google Scholar 

  36. Pryzhkova MV. Concise review: carbon nanotechnology: perspectives in stem cell research. Stem Cells Trans Med. 2013;2:376–83.

    Article  CAS  Google Scholar 

  37. Musumeci T, Pellitteri R, Spatuzza M, Puglisi G. Nose-to-brain delivery: evaluation of polymeric nanoparticles on olfactory ensheathing cells uptake. J Pharm Sci. 2014;103:628–35.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments and Disclosures

S.M. thanks the DAAD and Al-Quds University. G.C. thanks the financial support of Regional Operative Program (ROP) Calabria ESF 2007/2013IV Axis Human Capital Operative Objective M2 Action D.5. NHMRC Established Career Fellowship Award (M.K.). M.M. acknowledges financial support from the Excellence Cluster for Advancing Electronics Dresden (contract EXC1056). We thank Steffi Kaschube, Marco Rosenkranz, David Kunhard, and Alexander Schubert for lab assistance. O.V. thanks the Cancer Institute New South Wales Fellowship.

Author information

Authors and Affiliations

  1. Leibniz Institute for Solid State and Materials Research Dresden, 01171, Dresden, Germany

    Sami Makharza, Giuseppe Cirillo, Steffen Oswald, Bernd Büchner & Silke Hampel

  2. Department of physical chemistry, Technische Universität Dresden, 01062, Dresden, Germany

    Michael Mertig

  3. Children’s Cancer Institute Australia, Lowy Cancer Research Centre, University of New South Wales, NSW, Sydney, Australia

    Orazio Vittorio & Maria Kavallaris

  4. Australian Centre for NanoMedicine, University of New South Wales, NSW, Sydney, Australia

    Orazio Vittorio, Elizabeth Hinde & Maria Kavallaris

  5. Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036, Rende, (CS), Italy

    Giuseppe Cirillo

  6. ARC Centre of Excellence in Advanced Molecular Imaging, University of New South Wales, Sydney, Australia

    Elizabeth Hinde & Maria Kavallaris

  7. Department of Physics, 01062, Technische Universität Dresden, Dresden, Germany

    Bernd Büchner

  8. Kurt Schwabe Institute for Sensor Technology, 04736, Waldheim, Germany

    Michael Mertig

Authors
  1. Sami Makharza
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  2. Orazio Vittorio
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Corresponding authors

Correspondence to Sami Makharza or Giuseppe Cirillo.

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Makharza, S., Vittorio, O., Cirillo, G. et al. Graphene Oxide - Gelatin Nanohybrids as Functional Tools for Enhanced Carboplatin Activity in Neuroblastoma Cells. Pharm Res 32, 2132–2143 (2015). https://doi.org/10.1007/s11095-014-1604-z

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  • DOI: https://doi.org/10.1007/s11095-014-1604-z

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