The radiosensitization of melanoma cells by gold nanorods irradiated with MV X-ray

Melanoma is known to be radioresistant and traditional treatments have been intractable, and therefore, novel approaches are required to improve therapeutic efficacy. Gold nanoparticles (GNPs) have been explored as radiosensitizers, while most of the research in the area has focused on the enhancement occurred in the kilovoltage (kV ) range. The present study investigated the possible application and biological mechanism of gold nanorods (GNRs) for sensitization at clinically relevant MV X-ray energies. A375 melanoma cells were treated by gold nanorods (GNRs) with or without irradiation. The anti-proliferative impacts of the treatments were measured by MTT assay. The cellular uptake and intracellular localization were analyzed by transmission electron microscopy. Radiosensitizing effects were determined by a colony formation assay. Apoptosis and cell cycle data were measured by flow cytometry. DNA damage was estimated by γ-H2AX expression measured with immunofluorescent staining. Results showed that the addition of GNRs enhanced the radiosensitivity of A375 cells with a dose-modifying factor (DMFSF2) of 1.14, increasing more radiation-induced DNA double-strand breaks and apoptosis. DNA flow cytometric analysis indicated that GNRs plus irradiation significantly induced G2/M phase arrest in A375 cells. In Conclusions: GNRs could sensitize melanoma A375 cells to 6 MV X-ray irradiation, and this was mainly through increasing the DNA doublestrand breaks, in addition to the induction of a higher proportion of cells within the G2/M phase. The interaction of GNRs and high energy commonly used in the clinic may provides another rational for the potential application of GNRs in the treatment of cancer..

[1]  Weipeng Cao,et al.  Gold nanoparticles functionalized with therapeutic and targeted peptides for cancer treatment. , 2012, Biomaterials.

[2]  Daxiang Cui,et al.  Folic acid-conjugated silica-modified gold nanorods for X-ray/CT imaging-guided dual-mode radiation and photo-thermal therapy. , 2011, Biomaterials.

[3]  Peng Huang,et al.  Enhancement of gastric cell radiation sensitivity by chitosan-modified gold nanoparticles. , 2011, Journal of nanoscience and nanotechnology.

[4]  J. Pignol,et al.  Implications on clinical scenario of gold nanoparticle radiosensitization in regards to photon energy, nanoparticle size, concentration and location , 2011, Physics in medicine and biology.

[5]  Jie Chen,et al.  Thio-glucose bound gold nanoparticles enhance radio-cytotoxic targeting of ovarian cancer , 2011, Nanotechnology.

[6]  S. Singh,et al.  Functionalized Gold Nanoparticles and Their Biomedical Applications , 2011, Nanomaterials.

[7]  H. Gogas,et al.  Melanoma: the radiotherapeutic point of view; review of the current literature. , 2011, Reviews on recent clinical trials.

[8]  Jean-Philippe Pignol,et al.  Design and characterization of HER-2-targeted gold nanoparticles for enhanced X-radiation treatment of locally advanced breast cancer. , 2010, Molecular pharmaceutics.

[9]  Sailing He,et al.  Enhancing fluorescence of quantum dots by silica-coated gold nanorods under one- and two-photon excitation. , 2010, Optics express.

[10]  Kan Wang,et al.  Electrochemical Property and Cell Toxicity of Gold Electrode Modified by Monolayer PAMAM Encapsulated Gold Nanorods , 2010 .

[11]  Salomeh Jelveh,et al.  Gold Nanoparticles as Radiation Sensitizers in Cancer Therapy , 2010, Radiation research.

[12]  Markus Löbrich,et al.  γH2AX foci analysis for monitoring DNA double-strand break repair: Strengths, limitations and optimization , 2010, Cell cycle.

[13]  Xin Li,et al.  A study of mesoporous silica-encapsulated gold nanorods as enhanced light scattering probes for cancer cell imaging , 2010, Nanotechnology.

[14]  Nengqin Jia,et al.  Gold Nanorods Coated with Multilayer Polyelectrolyte as Intracellular delivery Vector of Antisense Oligonucleotides , 2010 .

[15]  Jie Chen,et al.  Enhancement of radiation cytotoxicity in breast-cancer cells by localized attachment of gold nanoparticles. , 2008, Small.

[16]  S. Santra,et al.  Silica-based multimodal/multifunctional nanoparticles for bioimaging and biosensing applications. , 2008, Nanomedicine.

[17]  Yi Zheng,et al.  Radiosensitization of DNA by Gold Nanoparticles Irradiated with High-Energy Electrons , 2008, Radiation research.

[18]  G. Cuttone,et al.  Response of a Human Melanoma Cell Line to Low and High Ionizing Radiation , 2007, Annals of the New York Academy of Sciences.

[19]  H. Maeda,et al.  Exploiting the enhanced permeability and retention effect for tumor targeting. , 2006, Drug discovery today.

[20]  Wei Chen,et al.  Using nanoparticles to enable simultaneous radiation and photodynamic therapies for cancer treatment. , 2006, Journal of nanoscience and nanotechnology.

[21]  Feng Gao,et al.  End-to-end self-assembly and colorimetric characterization of gold nanorods and nanospheres via oligonucleotide hybridization , 2005 .

[22]  J. Hainfeld,et al.  The use of gold nanoparticles to enhance radiotherapy in mice. , 2004, Physics in medicine and biology.

[23]  Stephen J Kron,et al.  Histone H2AX Phosphorylation as a Predictor of Radiosensitivity and Target for Radiotherapy* , 2004, Journal of Biological Chemistry.

[24]  B. Pak,et al.  Radiation resistance of human melanoma analysed by retroviral insertional mutagenesis reveals a possible role for dopachrome tautomerase , 2004, Oncogene.

[25]  P. Olive,et al.  Expression of phosphorylated histone H2AX in cultured cell lines following exposure to X‐rays , 2003, International journal of radiation biology.

[26]  J. Robar,et al.  Tumour dose enhancement using modified megavoltage photon beams and contrast media. , 2002, Physics in medicine and biology.

[27]  Catherine J. Murphy,et al.  CONTROLLING THE ASPECT RATIO OF INORGANIC NANORODS AND NANOWIRES , 2002 .

[28]  E. Rogakou,et al.  Quantitative detection of (125)IdU-induced DNA double-strand breaks with gamma-H2AX antibody. , 2002, Radiation research.

[29]  Y. Koyanagi,et al.  Direct measurement of the extravasation of polyethyleneglycol-coated liposomes into solid tumor tissue by in vivo fluorescence microscopy , 1996 .

[30]  W. K. Sinclair.  Cyclic x-ray responses in mammalian cells in vitro. , 1968, Radiation research.

[31]  F. Spiers.  The influence of energy absorption and electron range on dosage in irradiated bone. , 1949, The British journal of radiology.