A theranostic prodrug delivery system based on Pt(IV) conjugated nano-graphene oxide with synergistic effect to enhance the therapeutic efficacy of Pt drug

Biomaterials. 2015 May:51:12-21. doi: 10.1016/j.biomaterials.2015.01.074. Epub 2015 Feb 14.

Abstract

Due to their high NIR-optical absorption and high specific surface area, graphene oxide and graphene oxide-based nanocomposites have great potential in both drug delivery and photothermal therapy. In the work reported herein we successfully integrate a Pt(IV) complex (c,c,t-[Pt(NH3)2Cl2(OH)2]), PEGylated nano-graphene oxide (PEG-NGO), and a cell apoptosis sensor into a single platform to generate a multifunctional nanocomposite (PEG-NGO-Pt) which shows potential for targeted drug delivery and combined photothermal-chemotherapy under near infrared laser irradiation (NIR), and real-time monitoring of its therapeutic efficacy. Non-invasive imaging using a fluorescent probe immobilized on the GO shows an enhanced therapeutic effect of PEG-NGO-Pt in cancer treatment via apoptosis and cell death. Due to the enhanced cytotoxicity of cisplatin and the highly specific tumor targeting of PEG-NGO-Pt at elevated temperatures, this nanocomposite displays a synergistic effect in improving the therapeutic efficacy of the Pt drug with complete destruction of tumors, no tumor recurrence and minimal systemic toxicity in comparison with chemotherapy or photothermal treatment alone, highlighting the advantageous effects of integrating Pt(IV) with GO for anticancer treatment.

Keywords: Graphene oxide; Photothermal; Pt(IV); Synergistic; Theranostic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Death
  • Cell Line, Tumor
  • Drug Delivery Systems*
  • Drug Liberation
  • Drug Synergism
  • Female
  • Graphite / chemistry*
  • Humans
  • Hydrogen-Ion Concentration
  • Mice
  • Microscopy, Atomic Force
  • Nanocomposites / chemistry
  • Organ Specificity / drug effects
  • Oxides / chemistry*
  • Phototherapy
  • Platinum / pharmacology
  • Platinum / therapeutic use*
  • Polyethylene Glycols / chemical synthesis
  • Polyethylene Glycols / chemistry
  • Prodrugs / pharmacology
  • Prodrugs / therapeutic use*
  • Spectrometry, Fluorescence
  • Theranostic Nanomedicine*
  • Xenograft Model Antitumor Assays

Substances

  • Oxides
  • Prodrugs
  • Polyethylene Glycols
  • Platinum
  • Graphite