A tumor-targeting near-infrared laser-triggered drug delivery system based on GO@Ag nanoparticles for chemo-photothermal therapy and X-ray imaging

Biomaterials. 2014 Jul;35(22):5847-61. doi: 10.1016/j.biomaterials.2014.03.042. Epub 2014 Apr 17.

Abstract

In this study, a GO@Ag nanocomposite was synthesized by chemical deposition of Ag nanoparticles onto graphene oxide (GO) through a hydro thermal reaction, and doxorubicin (DOX), one of the most effective drugs against a wide range of cancers, was employed as the model drug and linked to GO@Ag via ester bonds with a very high drug loading efficiency (∼82.0%, weight ratio of DOX/GO@Ag), then GO@Ag-DOX was functionalized by DSPE-PEG2000-NGR, giving GO@Ag-DOX with active tumor-targeting capacity and excellent stability in physiological solutions. The release profiles of DOX from GO@Ag-DOX-NGR showed strong dependences on near-infrared (NIR) laser and the SPR effect of Ag nanoparticles. Compared with free DOX in an in vivo murine tumor model, GO@Ag-DOX-NGR afforded much higher antitumor efficacy without obvious toxic effects to normal organs owing to 8.4-fold higher DOX uptake of tumor and 1.7-fold higher DOX released in tumor with NIR laser than the other tissues. Besides, in this work, GO@Ag-DOX-NGR not only served as a powerful tumor diagnostic X-ray contrast agent, but also as a strong agent for photothermal ablation of tumor, the ability of GO@Ag-DOX-NGR nanoparticles to combine the local specific chemotherapy with external photothermal therapy (PTT) significantly improved the therapeutic efficacy. GO@Ag-DOX-NGR showed excellent chem-photothermal therapeutic efficacy, tumor-targeting property, NIR laser-controlled drug releasing function and X-ray imaging ability, demonstrating that there is a great potential of GO@Ag-DOX-NGR for cancer diagnosis and therapy.

Keywords: Controlled drug release; GO@Ag; Tumor-targeting; X-ray imaging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / administration & dosage
  • Antibiotics, Antineoplastic / therapeutic use
  • Cell Line, Tumor
  • Doxorubicin / administration & dosage
  • Doxorubicin / therapeutic use
  • Drug Delivery Systems / methods
  • Graphite / chemistry
  • Graphite / therapeutic use*
  • Humans
  • Hyperthermia, Induced
  • Lasers
  • Mice
  • Nanoparticles / chemistry
  • Nanoparticles / therapeutic use*
  • Neoplasms / diagnostic imaging
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • Oxides / chemistry
  • Oxides / therapeutic use
  • Phosphatidylethanolamines / chemistry
  • Phosphatidylethanolamines / therapeutic use
  • Phototherapy
  • Polyethylene Glycols / chemistry
  • Polyethylene Glycols / therapeutic use
  • Silver / chemistry
  • Silver / therapeutic use*
  • Tomography, X-Ray Computed
  • Xenograft Model Antitumor Assays

Substances

  • 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000)
  • Antibiotics, Antineoplastic
  • Oxides
  • Phosphatidylethanolamines
  • Silver
  • Polyethylene Glycols
  • Graphite
  • Doxorubicin