Surface modified magnetic nanoparticles for immuno-gene therapy of murine mammary adenocarcinoma

Biomaterials. 2012 Jun;33(17):4379-91. doi: 10.1016/j.biomaterials.2012.02.061. Epub 2012 Mar 18.

Abstract

Cancer immuno-gene therapy is an introduction of nucleic acids encoding immunostimulatory proteins, such as cytokine interleukin 12 (IL-12), into somatic cells to stimulate an immune response against a tumor. Various methods can be used for the introduction of nucleic acids into cells; magnetofection involves binding of nucleic acids to magnetic nanoparticles with subsequent exposure to an external magnetic field. Here we show that surface modified superparamagnetic iron oxide nanoparticles (SPIONs) with a combination of polyacrylic acid (PAA) and polyethylenimine (PEI) (SPIONs-PAA-PEI) proved to be safe and effective for magnetofection of cells and tumors in mice. Magnetofection of cells with plasmid DNA encoding reporter gene using SPIONs-PAA-PEI was superior in transfection efficiency to commercially available SPIONs. Magnetofection of murine mammary adenocarcinoma with plasmid DNA encoding IL-12 using SPIONs-PAA-PEI resulted in significant antitumor effect and could be further refined for cancer immuno-gene therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrylic Resins / toxicity
  • Adenocarcinoma / pathology
  • Adenocarcinoma / therapy*
  • Animals
  • Body Weight / drug effects
  • Cell Death / drug effects
  • Cell Line
  • Cell Line, Tumor
  • DNA / metabolism
  • Endocytosis / drug effects
  • Female
  • Genetic Therapy / methods*
  • Humans
  • Immunotherapy / methods*
  • Injections, Intraperitoneal
  • Interleukin-12 / administration & dosage
  • Interleukin-12 / pharmacology
  • Magnetite Nanoparticles / administration & dosage
  • Magnetite Nanoparticles / chemistry*
  • Magnetite Nanoparticles / toxicity
  • Magnetite Nanoparticles / ultrastructure
  • Mammary Neoplasms, Animal / pathology
  • Mammary Neoplasms, Animal / therapy*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Plasmids / metabolism
  • Polyethyleneimine / toxicity
  • Surface Properties / drug effects
  • Tissue Distribution / drug effects
  • Transfection

Substances

  • Acrylic Resins
  • Magnetite Nanoparticles
  • Interleukin-12
  • carbopol 940
  • Polyethyleneimine
  • DNA