Functional graphene oxide as a nanocarrier for controlled loading and targeted delivery of mixed anticancer drugs.

A simple synthetic route for the preparation of functional nanoscale graphene oxide (NGO), a novel nanocarrier for the loading and targeted delivery of anticancer drugs, is reported. The NGO is functionalized with sulfonic acid groups, which render it stable in physiological solution, followed by covalent binding of folic acid (FA) molecules to the NGO, thus allowing it to specifically target MCF-7 cells, human breast cancer cells with FA receptors. Furthermore, controlled loading of two anticancer drugs, doxorubicin (DOX) and camptothecin (CPT), onto the FA-conjugated NGO (FA-NGO) via pi-pi stacking and hydrophobic interactions is investigated. It is demonstrated that FA-NGO loaded with the two anticancer drugs shows specific targeting to MCF-7 cells, and remarkably high cytotoxicity compared to NGO loaded with either DOX or CPT only. Considering that the combined use of two or more drugs, a widely adopted clinical practice, often displays much better therapeutic efficacy than that of a single drug, the controlled loading and targeted delivery of mixed anticancer drugs using these graphene-based nanocarriers may find widespread application in biomedicine.

[1]  R. Ramanujan,et al.  Thermoresponsive magnetic composite nanomaterials for multimodal cancer therapy. , 2010, Acta biomaterialia.

[2]  A. Srivastava,et al.  A facile and novel synthesis of Ag-graphene-based nanocomposites. , 2009, Small.

[3]  Lain‐Jong Li,et al.  Photoelectrical response in single-layer graphene transistors. , 2009, Small.

[4]  Jan Grimm,et al.  Drug/dye-loaded, multifunctional iron oxide nanoparticles for combined targeted cancer therapy and dual optical/magnetic resonance imaging. , 2009, Small.

[5]  Yongsheng Chen,et al.  Photoconductivity of bulk-film-based graphene sheets. , 2009, Small.

[6]  G. Wallace,et al.  Electrochemical Properties of Graphene Paper Electrodes Used in Lithium Batteries , 2009 .

[7]  Yang Li,et al.  Shell-detachable micelles based on disulfide-linked block copolymer as potential carrier for intracellular drug delivery. , 2009, Bioconjugate chemistry.

[8]  Baorui Liu,et al.  Dual-functional alginic acid hybrid nanospheres for cell imaging and drug delivery. , 2009, Small.

[9]  F. Guinea,et al.  The electronic properties of graphene , 2007, Reviews of Modern Physics.

[10]  Guoliang Zhang,et al.  Deoxygenation of Exfoliated Graphite Oxide under Alkaline Conditions: A Green Route to Graphene Preparation , 2008 .

[11]  T. McLeish,et al.  Preparation of hierarchical hollow CaCO3 particles and the application as anticancer drug carrier. , 2008, Journal of the American Chemical Society.

[12]  Yongsheng Chen,et al.  High-Efficiency Loading and Controlled Release of Doxorubicin Hydrochloride on Graphene Oxide , 2008 .

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

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

[15]  E. Samulski,et al.  Synthesis of water soluble graphene. , 2008, Nano letters.

[16]  H. Dai,et al.  Chemically Derived, Ultrasmooth Graphene Nanoribbon Semiconductors , 2008, Science.

[17]  R. Stoltenberg,et al.  Evaluation of solution-processed reduced graphene oxide films as transparent conductors. , 2008, ACS nano.

[18]  G. Wallace,et al.  Processable aqueous dispersions of graphene nanosheets. , 2008, Nature nanotechnology.

[19]  John W. Park,et al.  Convection-enhanced delivery of nanoliposomal CPT-11 (irinotecan) and PEGylated liposomal doxorubicin (Doxil) in rodent intracranial brain tumor xenografts. , 2007, Neuro-oncology.

[20]  Hongjie Dai,et al.  Supramolecular Chemistry on Water- Soluble Carbon Nanotubes for Drug Loading and Delivery , 2007 .

[21]  R. Hamilton,et al.  A comparison of dispersing media for various engineered carbon nanoparticles , 2007, Particle and Fibre Toxicology.

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

[23]  S. Stankovich,et al.  Graphene-based composite materials , 2006, Nature.

[24]  S. Shany,et al.  The combined treatment of 1,25-dihydroxyvitamin D3 and a non-steroid anti-inflammatory drug is highly effective in suppressing prostate cancer cell line (LNCaP) growth. , 2005, Anticancer research.

[25]  Paras N Prasad,et al.  Folate-receptor-mediated delivery of InP quantum dots for bioimaging using confocal and two-photon microscopy. , 2005, Journal of the American Chemical Society.

[26]  M. Prato,et al.  Novel Photoactive Single‐Walled Carbon Nanotube–Porphyrin Polymer Wraps: Efficient and Long‐Lived Intracomplex Charge Separation , 2005 .

[27]  Y. Kobuke,et al.  Porphyrin−Carbon Nanotube Composites Formed by Noncovalent Polymer Wrapping , 2005 .

[28]  Koert N. J. Burger,et al.  Nanocapsules: lipid-coated aggregates of cisplatin with high cytotoxicity , 2002, Nature Medicine.

[29]  P. J. Ollivier,et al.  Layer-by-Layer Assembly of Ultrathin Composite Films from Micron-Sized Graphite Oxide Sheets and Polycations , 1999 .

[30]  H. Mouridsen,et al.  Doxorubicin versus methotrexate both combined with cyclophosphamide, 5-fluorouracil and tamoxifen in postmenopausal patients with advanced breast cancer--a randomised study with more than 10 years follow-up from the Danish Breast Cancer Cooperative Group. Danish Breast Cancer Cooperative Group (DBCG , 1999, European journal of cancer.

[31]  T. Okano,et al.  Characterization of physical entrapment and chemical conjugation of adriamycin in polymeric micelles and their design for in vivo delivery to a solid tumor. , 1998, Journal of controlled release : official journal of the Controlled Release Society.

[32]  A. C. Dubbelman,et al.  Phase I and pharmacological study of sequential intravenous topotecan and oral etoposide. , 1997, British Journal of Cancer.