Exceedingly Higher co-loading of Curcumin and Paclitaxel onto Polymer-functionalized Reduced Graphene Oxide for Highly Potent Synergistic Anticancer Treatment

Sci Rep. 2016 Sep 6:6:32808. doi: 10.1038/srep32808.

Abstract

Metastasis of lung carcinoma to breast and vice versa accounts for one of the vast majority of cancer deaths. Synergistic treatments are proven to be the effective method to inhibit malignant cell proliferation. It is highly advantageous to use the minimum amount of a potent toxic drug, such as paclitaxel (Ptx) in ng/ml together with a natural and safe anticancer drug, curcumin (Cur) to reduce the systemic toxicity. However, both Cur and Ptx suffer from poor bioavailability. Herein, a drug delivery cargo was engineered by functionalizing reduced graphene oxide (G) with an amphiphilic polymer, PF-127 (P) by hydrophobic assembly. The drugs were loaded via pi-pi interactions, resulting in a nano-sized GP-Cur-Ptx of 140 nm. A remarkably high Cur loading of 678 wt.% was achieved, the highest thus far compared to any other Cur nanoformulations. Based on cell proliferation assay, GP-Cur-Ptx is a synergistic treatment (CI < 1) and is highly potent towards lung, A549 (IC50 = 13.24 μg/ml) and breast, MDA-MB-231 (IC50 = 1.450 μg/ml) cancer cells. These positive findings are further confirmed by increased reactive oxygen species, mitochondrial membrane potential depletion and cell apoptosis. The same dose treated on normal MRC-5 cells shows that the system is biocompatible and cancerous cell-specific.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Curcumin / chemistry*
  • Curcumin / pharmacology
  • Drug Carriers / chemistry
  • Drug Delivery Systems / methods
  • Drug Synergism
  • Female
  • Graphite / chemistry*
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / metabolism
  • Membrane Potential, Mitochondrial / drug effects
  • Nanoparticles / chemistry
  • Oxides / chemistry*
  • Paclitaxel / chemistry*
  • Paclitaxel / pharmacology
  • Polymers / chemistry*
  • Reactive Oxygen Species / metabolism

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Oxides
  • Polymers
  • Reactive Oxygen Species
  • Graphite
  • Curcumin
  • Paclitaxel