Gelatin-encapsulated iron oxide nanoparticles for platinum (IV) prodrug delivery, enzyme-stimulated release and MRI

Biomaterials. 2014 Aug;35(24):6359-68. doi: 10.1016/j.biomaterials.2014.04.029. Epub 2014 May 9.

Abstract

A facile method for transferring hydrophobic iron oxide nanoparticles (IONPs) from chloroform to aqueous solution via encapsulation of FITC-modified gelatin based on the hydrophobic-hydrophobic interaction is described in this report. Due to the existence of large amount of active groups such as amine groups in gelatin, the fluorescent labeling molecules of fluorescein isothiocyanate (FITC) and platinum (IV) prodrug functionalized with carboxylic groups can be conveniently conjugated on the IONPs. The nanoparticles carrying Pt(IV) prodrug exhibit good anticancer activities when the Pt(IV) complexes are reduced to Pt(II) in the intracellular environment, while the pure Pt(IV) prodrug only presents lower cytotoxicity on cancer cells. Meanwhile, fluorescence of FITC on the surface of nanoparticles was completely quenched due to the possible Förster Resonance Energy Transfer (FRET) mechanism and showed a fluorescence recovery after gelatin release and detachment from IONPs. Therefore FITC as a fluorescence probe can be used for identification, tracking and monitoring the drug release. In addition, adding pancreatic enzyme can effectively promote the gelatin release from IONPs owing to the degradation of gelatin. Noticeable darkening in magnetic resonance image (MRI) was observed at the tumor site after in situ injection of nanoparticles, indicating the IONPs-enhanced T2-weighted imaging. Our results suggest that the gelatin encapsulated Fe3O4 nanoparticles have potential applications in multi-functional drug delivery system for disease therapy, MR imaging and fluorescence sensor.

Keywords: Fluorescence quenching; Gelatin encapsulation; Iron oxide; Magnetic resonance imaging; Platinum (IV) prodrug.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Survival / drug effects
  • Drug Delivery Systems*
  • Ferric Compounds / chemistry*
  • Fluorescein-5-isothiocyanate / metabolism
  • Gelatin / chemistry*
  • Humans
  • Hydrophobic and Hydrophilic Interactions / drug effects
  • MCF-7 Cells
  • Magnetic Resonance Imaging*
  • Mice
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Pancreatin / metabolism*
  • Particle Size
  • Photoelectron Spectroscopy
  • Platinum / administration & dosage*
  • Platinum / pharmacology
  • Prodrugs / administration & dosage
  • Prodrugs / chemical synthesis
  • Prodrugs / chemistry
  • Prodrugs / pharmacology*
  • Spectrophotometry, Ultraviolet
  • Spectroscopy, Fourier Transform Infrared
  • Thermogravimetry
  • Tissue Distribution / drug effects
  • X-Ray Diffraction
  • Xenograft Model Antitumor Assays

Substances

  • Ferric Compounds
  • Prodrugs
  • ferric oxide
  • Platinum
  • Pancreatin
  • Gelatin
  • Fluorescein-5-isothiocyanate