Size-dependent cell uptake of protein-coated graphene oxide nanosheets.

As an emerging applied material, graphene has shown tremendous application potential in many fields, including biomedicine. However, the biological behavior of these nanosheets, especially their interactions with cells, is not well understood. Here, we report our findings about the cell surface adhesion, subcellular locations, and size-dependent uptake mechanisms of protein-coated graphene oxide nanosheets (PCGO). Small nanosheets enter cells mainly through clathrin-mediated endocytosis, and the increase of graphene size enhances phagocytotic uptake of the nanosheets. These findings will facilitate biomedical and toxicologic studies of graphenes and provide fundamental understanding of interactions at the interface of two-dimensional nanostructures and biological systems.

[1]  Bing Yan,et al.  Enhancing cell recognition by scrutinizing cell surfaces with a nanoparticle array. , 2011, Journal of the American Chemical Society.

[2]  Huajian Gao,et al.  Cell entry of one-dimensional nanomaterials occurs by tip recognition and rotation. , 2011, Nature nanotechnology.

[3]  A. Asano,et al.  Synergistic effect of colchicine and cytochalasin D on phagocytosis by peritoneal macrophages , 1976, Nature.

[4]  A. Tsourkas,et al.  Size, charge and concentration dependent uptake of iron oxide particles by non-phagocytic cells. , 2008, Biomaterials.

[5]  C. Röcker,et al.  Endo- and exocytosis of zwitterionic quantum dot nanoparticles by live HeLa cells. , 2010, ACS nano.

[6]  Lei Yang,et al.  Enhancement of cell recognition in vitro by dual-ligand cancer targeting gold nanoparticles. , 2011, Biomaterials.

[7]  Zhijun Zhang,et al.  Functional graphene oxide as a nanocarrier for controlled loading and targeted delivery of mixed anticancer drugs. , 2010, Small.

[8]  Taosheng Chen,et al.  Suppression of human bone morphogenetic protein signaling by carboxylated single-walled carbon nanotubes. , 2009, ACS nano.

[9]  Warren C W Chan,et al.  Elucidating the mechanism of cellular uptake and removal of protein-coated gold nanoparticles of different sizes and shapes. , 2007, Nano letters.

[10]  Zhuang Liu,et al.  Nano-graphene oxide for cellular imaging and drug delivery , 2008, Nano research.

[11]  Andre K. Geim,et al.  The rise of graphene. , 2007, Nature materials.

[12]  C. Yi,et al.  Gold nanoparticles promote osteogenic differentiation of mesenchymal stem cells through p38 MAPK pathway. , 2010, ACS nano.

[13]  Yang Li,et al.  Disposable biosensor based on graphene oxide conjugated with tyrosinase assembled gold nanoparticles. , 2011, Biosensors & bioelectronics.

[14]  Kai Yang,et al.  The influence of surface chemistry and size of nanoscale graphene oxide on photothermal therapy of cancer using ultra-low laser power. , 2012, Biomaterials.

[15]  Jinbin Liu,et al.  Toward a universal "adhesive nanosheet" for the assembly of multiple nanoparticles based on a protein-induced reduction/decoration of graphene oxide. , 2010, Journal of the American Chemical Society.

[16]  M. Prato,et al.  Functionalized carbon nanotubes for plasmid DNA gene delivery. , 2004, Angewandte Chemie.

[17]  Na Zhang,et al.  Enhanced gene transfection efficiency in CD13-positive vascular endothelial cells with targeted poly(lactic acid)-poly(ethylene glycol) nanoparticles through caveolae-mediated endocytosis. , 2011, Journal of controlled release : official journal of the Controlled Release Society.

[18]  Kai Yang,et al.  Graphene in mice: ultrahigh in vivo tumor uptake and efficient photothermal therapy. , 2010, Nano letters.

[19]  Moonjung Choi,et al.  Cellular uptake, cytotoxicity, and innate immune response of silica-titania hollow nanoparticles based on size and surface functionality. , 2010, ACS nano.

[20]  Zhouyi Guo,et al.  Synergistic effect of chemo-photothermal therapy using PEGylated graphene oxide. , 2011, Biomaterials.

[21]  Liangzhu Feng,et al.  Graphene in biomedicine: opportunities and challenges. , 2011, Nanomedicine.

[22]  Yanli Chang,et al.  In vitro toxicity evaluation of graphene oxide on A549 cells. , 2011, Toxicology letters.

[23]  C. Dani,et al.  Macrophage characteristics of stem cells revealed by transcriptome profiling. , 2006, Experimental cell research.

[24]  Bing Yan,et al.  Endosomal leakage and nuclear translocation of multiwalled carbon nanotubes: developing a model for cell uptake. , 2009, Nano letters.

[25]  C. Fan,et al.  Protein corona-mediated mitigation of cytotoxicity of graphene oxide. , 2011, ACS nano.

[26]  R. G. Anderson,et al.  Mis-assembly of clathrin lattices on endosomes reveals a regulatory switch for coated pit formation , 1993, The Journal of cell biology.

[27]  F. Porta,et al.  Phagocytosis of biocompatible gold nanoparticles. , 2010, Langmuir : the ACS journal of surfaces and colloids.

[28]  G. Jiang,et al.  Leading neuroblastoma cells to die by multiple premeditated attacks from a multifunctionalized nanoconstruct. , 2011, Journal of the American Chemical Society.

[29]  Michael S. Strano,et al.  Size-dependent cellular uptake and expulsion of single-walled carbon nanotubes: single particle tracking and a generic uptake model for nanoparticles. , 2009, ACS nano.

[30]  M. Prato,et al.  Cellular uptake of functionalized carbon nanotubes is independent of functional group and cell type. , 2007, Nature nanotechnology.