Raman spectroscopy for the detection of organ distribution and clearance of PEGylated reduced graphene oxide and biological consequences.

Graphene, a 2D carbon material has found vast application in biomedical field because of its exciting physico-chemical properties. The large planar sheet like structure helps graphene to act as an effective carrier of drug or biomolecules in enormous amount. However, limited data available on the biocompatibility of graphene upon interaction with the biological system prompts us to evaluate their toxicity in animal model. In this study organ distribution, clearance and toxicity of PEGylated reduced nanographene (PrGO) on Swiss Albino mice was investigated after intraperitoneal and intravenous administration. Biodistribution and blood clearance was monitored using confocal Raman mapping and indicated that PrGO was distributed on major organs such as brain, liver, kidney, spleen and bone marrow. Presence of PrGO in brain tissue suggests that it has the potential to cross blood brain barrier. Small amount of injected PrGO was found to excrete via urine. Repeated administration of PrGO induced acute liver injury, congestion in kidney and increased splenocytes proliferation in days following exposure. Hence the result of the study recommended that PrGO should undergo intensive safety assessment before clinical application or validated to be safe for medical use.

[1]  B. van Ravenzwaay,et al.  Comparative inhalation toxicity of multi-wall carbon nanotubes, graphene, graphite nanoplatelets and low surface carbon black , 2013, Particle and Fibre Toxicology.

[2]  Zhuang Liu,et al.  PEGylated nanographene oxide for delivery of water-insoluble cancer drugs. , 2008, Journal of the American Chemical Society.

[3]  Balaji Sitharaman,et al.  Cell specific cytotoxicity and uptake of graphene nanoribbons. , 2013, Biomaterials.

[4]  H. Dai,et al.  PEG branched polymer for functionalization of nanomaterials with ultralong blood circulation. , 2009, Journal of the American Chemical Society.

[5]  Kai Yang,et al.  Functionalization of graphene oxide generates a unique interface for selective serum protein interactions. , 2013, ACS applied materials & interfaces.

[6]  Jie Huang,et al.  Polyethylenimine-functionalized graphene oxide as an efficient gene delivery vector , 2011 .

[7]  N. Chatterjee,et al.  A systems toxicology approach to the surface functionality control of graphene-cell interactions. , 2014, Biomaterials.

[8]  Debabrata Dash,et al.  Amine-modified graphene: thrombo-protective safer alternative to graphene oxide for biomedical applications. , 2012, ACS nano.

[9]  A. Pandey,et al.  Toxicity of graphene in normal human lung cells (BEAS-2B). , 2011, Journal of biomedical nanotechnology.

[10]  Lifeng Yan,et al.  Chemical Reduction of Graphene Oxide to Graphene by Sulfur-Containing Compounds , 2010 .

[11]  L. Yin,et al.  Contributions of altered permeability of intestinal barrier and defecation behavior to toxicity formation from graphene oxide in nematode Caenorhabditis elegans. , 2013, Nanoscale.

[12]  N. Mei,et al.  Assessment of the toxic potential of graphene family nanomaterials , 2014, Journal of food and drug analysis.

[13]  Yanli Chang,et al.  Effect of size and dose on the biodistribution of graphene oxide in mice. , 2012, Nanomedicine.

[14]  B. Hong,et al.  Biomedical applications of graphene and graphene oxide. , 2013, Accounts of chemical research.

[15]  A. Rao,et al.  Intravenously delivered graphene nanosheets and multiwalled carbon nanotubes induce site-specific Th2 inflammatory responses via the IL-33/ST2 axis , 2013, International journal of nanomedicine.

[16]  Chunhai Fan,et al.  Distribution and biocompatibility studies of graphene oxide in mice after intravenous administration , 2011 .

[17]  M. Taghioskoui Trends in graphene research , 2009 .

[18]  Ying Liu,et al.  The triggering of apoptosis in macrophages by pristine graphene through the MAPK and TGF-beta signaling pathways. , 2012, Biomaterials.

[19]  Ken Donaldson,et al.  Graphene-based nanoplatelets: a new risk to the respiratory system as a consequence of their unusual aerodynamic properties. , 2012, ACS nano.

[20]  Mark C Hersam,et al.  Minimizing oxidation and stable nanoscale dispersion improves the biocompatibility of graphene in the lung. , 2011, Nano letters.

[21]  Waqar Ahmed,et al.  PEGylated graphene oxide for tumor-targeted delivery of paclitaxel. , 2015, Nanomedicine.

[22]  He Shen,et al.  Biomedical Applications of Graphene , 2012, Theranostics.

[23]  Lei Tao,et al.  A comparative study of cellular uptake and cytotoxicity of multi-walled carbon nanotubes, graphene oxide, and nanodiamond , 2012 .

[24]  A. Ganguli,et al.  Enhanced functionalization of Mn2O3@SiO2 core-shell nanostructures , 2011, Nanoscale research letters.

[25]  Kai Yang,et al.  In vivo biodistribution and toxicology of functionalized nano-graphene oxide in mice after oral and intraperitoneal administration. , 2013, Biomaterials.

[26]  W. S. Hummers,et al.  Preparation of Graphitic Oxide , 1958 .

[27]  X. Xia,et al.  A green approach to the synthesis of graphene nanosheets. , 2009, ACS nano.

[28]  Andre K. Geim,et al.  Raman spectrum of graphene and graphene layers. , 2006, Physical review letters.

[29]  W. Duan,et al.  Role of surface charge and oxidative stress in cytotoxicity and genotoxicity of graphene oxide towards human lung fibroblast cells , 2013, Journal of applied toxicology : JAT.

[30]  Kai Yang,et al.  In vivo pharmacokinetics, long-term biodistribution, and toxicology of PEGylated graphene in mice. , 2011, ACS nano.

[31]  Deepthy Menon,et al.  Differential nano-bio interactions and toxicity effects of pristine versus functionalized graphene. , 2011, Nanoscale.

[32]  Jiali Zhang,et al.  Biocompatibility of Graphene Oxide , 2010, Nanoscale research letters.