Dimercaptosuccinic acid-coated magnetite nanoparticles for magnetically guided in vivo delivery of interferon gamma for cancer immunotherapy

Biomaterials. 2011 Apr;32(11):2938-52. doi: 10.1016/j.biomaterials.2011.01.008. Epub 2011 Jan 31.

Abstract

As radio- and chemotherapy-based cancer treatments affect both tumors and healthy tissue, cancer immunotherapy attempts to specifically enhance the natural immune response to tumor cells. In mouse models of cancer, we tested uniform dimercaptosuccinic acid (DMSA)-coated monodisperse magnetic nanoparticles as a delivery system for the anti-tumorigenic cytokine IFN-γ. IFN-γ-adsorbed DMSA-coated magnetic nanoparticles were targeted to the tumor site by application of an external magnetic field. We analyzed nanoparticle biodistribution before and after IFN-γ conjugation, as well as the efficiency of nanoparticle accumulation in tumors, IFN-γ release in the area of interest, and the effects of both on tumor development. At the tumor site, we observed a high degree of nanoparticle accumulation and of cytokine delivery, which led to increased T cell and macrophage infiltration and promoted an anti-angiogenic effect. The combined action led to a notable reduction in tumor size. Our findings indicate that IFN-γ-adsorbed DMSA-coated magnetite nanoparticles can be used as an efficient in vivo drug delivery system for tumor immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Female
  • Immunotherapy / methods*
  • Interferon-gamma / administration & dosage*
  • Interferon-gamma / blood
  • Interferon-gamma / therapeutic use*
  • Magnetite Nanoparticles / administration & dosage
  • Magnetite Nanoparticles / adverse effects
  • Magnetite Nanoparticles / chemistry*
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms / blood
  • Neoplasms / drug therapy*
  • Succimer / chemistry*
  • Succimer / therapeutic use*

Substances

  • Magnetite Nanoparticles
  • Interferon-gamma
  • Succimer