Porous hollow Fe(3)O(4) nanoparticles for targeted delivery and controlled release of cisplatin

J Am Chem Soc. 2009 Aug 5;131(30):10637-44. doi: 10.1021/ja903300f.

Abstract

We report a new approach to cisplatin storage and release using porous hollow nanoparticles (PHNPs) of Fe(3)O(4). We prepared the PHNPs by controlled oxidation of Fe NPs at 250 degrees C followed by acid etching. The opening pores ( approximately 2-4 nm) facilitated the cisplatin diffusion into the cavity of the hollow structure. The porous shell was stable in neutral or basic physiological conditions, and cisplatin escape from the cavity through the same pores was a diffusion-controlled slow process with t(1/2) = 16 h. However, in low pH (<6) conditions, the pores were subject to acidic etching, resulting in wider pore gaps and faster release of cisplatin with t(1/2) < 4 h. Once coupled with Herceptin to the surface, the cisplatin-loaded hollow NPs could target to breast cancer SK-BR-3 cells with IC(50) reaching 2.9 muM, much lower than 6.8 muM needed for free cisplatin. Our model experiments indicate that the low pH-responsive PHNPs of Fe(3)O(4) can be exploited as a cisplatin delivery vehicle for target-specific therapeutic applications.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Biological Transport
  • Cell Line, Tumor
  • Cisplatin / chemistry*
  • Cisplatin / metabolism*
  • Cisplatin / pharmacology
  • Delayed-Action Preparations / chemistry
  • Delayed-Action Preparations / metabolism
  • Delayed-Action Preparations / pharmacology
  • Diffusion
  • Drug Carriers / chemistry*
  • Ferrosoferric Oxide / chemistry*
  • Humans
  • Hydrogen-Ion Concentration
  • Inhibitory Concentration 50
  • Kinetics
  • Nanoparticles / chemistry*
  • Porosity
  • Surface Properties

Substances

  • Delayed-Action Preparations
  • Drug Carriers
  • Cisplatin
  • Ferrosoferric Oxide