cRGD-functionalized polymeric magnetic nanoparticles as a dual-drug delivery system for safe targeted cancer therapy

Pharmacol Res. 2013 Apr;70(1):102-15. doi: 10.1016/j.phrs.2013.01.009. Epub 2013 Jan 31.

Abstract

In this paper we give a method of integrated treatment for cancer and drug-induced complications in the process of cancer therapy through dual-drug delivery system (DDDS). Two hydrophilic drugs, doxorubicin (an antitumor drug) and verapamil (an antiangiocardiopathy drug) combined preliminarily with chitosan shell coated on magnetic nanoparticles (MNPs), followed by entrapping into the PLGA nanoparticles. Further modification was conducted by conjugating tumor-targeting ligand, cyclo(Arg-Gly-Asp-D-Phe-Lys) (c(RGDfK)) peptide, onto the end carboxyl groups on the PLGA-NPs. The size of the resulting cRGD-DOX/VER-MNP-PLGA NPs was approximately 144nm under simulate physiological environment. Under present experiment condition, the entrapment efficiencies of DOX and VER were approximately 74.8 and 53.2wt% for cRGD-DOX/VER-MNP-PLGA NPs. This paper contains interesting pilot data such as NIR-triggered drug release, in vivo drug distribution studies and whole-mouse optical imaging. Histopathological examinations and electrocardiogram comparison demonstrated that the intelligent DDDS could markedly inhibit the growth of tumor and potentially offer an approach for safe cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage*
  • Angiogenesis Inhibitors / pharmacokinetics
  • Angiogenesis Inhibitors / therapeutic use
  • Animals
  • Anti-Arrhythmia Agents / administration & dosage*
  • Anti-Arrhythmia Agents / pharmacokinetics
  • Anti-Arrhythmia Agents / therapeutic use
  • Cell Survival / drug effects
  • Doxorubicin / administration & dosage*
  • Doxorubicin / pharmacokinetics
  • Doxorubicin / therapeutic use
  • Drug Carriers / chemistry*
  • Drug Combinations
  • Drug Delivery Systems / methods
  • Electrocardiography
  • Hep G2 Cells
  • Humans
  • Lactic Acid / chemistry
  • Magnetite Nanoparticles / chemistry*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Particle Size
  • Peptides, Cyclic / administration & dosage*
  • Peptides, Cyclic / pharmacokinetics
  • Peptides, Cyclic / therapeutic use
  • Pilot Projects
  • Polyglycolic Acid / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Sarcoma, Experimental / drug therapy
  • Sarcoma, Experimental / metabolism
  • Sarcoma, Experimental / pathology
  • Solubility
  • Surface Properties
  • Tissue Distribution
  • Verapamil / administration & dosage*
  • Verapamil / pharmacokinetics
  • Verapamil / therapeutic use

Substances

  • Angiogenesis Inhibitors
  • Anti-Arrhythmia Agents
  • Drug Carriers
  • Drug Combinations
  • Magnetite Nanoparticles
  • Peptides, Cyclic
  • cyclic arginine-glycine-aspartic acid peptide
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Doxorubicin
  • Verapamil