Magnetic field contributes to the cellular uptake for effective therapy with magnetofection using plasmid DNA encoding against Mcam in B16F10 melanoma in vivo

Nanomedicine (Lond). 2016 Mar;11(6):627-41. doi: 10.2217/nnm.16.4. Epub 2016 Mar 8.

Abstract

Aim: We explored the distribution and cellular uptake of intratumorally injected SPIONs-PAA-PEI-pDNA (magnetofection complexes), and antitumor effectiveness of magnetofection with plasmid DNA encoding short hairpin RNA (shRNA) against Mcam (pDNA(anti-MCAM)).

Materials & methods: Analyses were made based on the histology, ultrastructure and quantitative measurements of magnetofection complexes, and quantification of the antitumor effectiveness in B16F10 melanoma in vivo.

Results: Injected magnetofection complexes were distributed around the injection site. Exposure of tumors to external magnetic field contributed to the uptake of magnetofection complexes from extracellular matrix into melanoma cells. Three consecutive magnetofections of tumors with pDNA(anti-MCAM) resulted in significant reduction of tumor volume.

Conclusion: Magnetofection is effective for gene delivery to melanoma tumors, but requires a magnetic field for cellular uptake and antitumor effect.

Keywords: MCAM; SPIONs; cellular uptake; intratumoral injection; magnetofection; murine melanoma tumor; therapeutic plasmid DNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD146 Antigen / genetics
  • Cell Line, Tumor
  • DNA / genetics
  • DNA / pharmacokinetics
  • DNA / therapeutic use*
  • Female
  • Gene Transfer Techniques*
  • Genetic Therapy / methods
  • Humans
  • Magnetic Fields
  • Magnetite Nanoparticles / chemistry
  • Melanoma / genetics
  • Melanoma / pathology
  • Melanoma / therapy*
  • Mice, Inbred C57BL
  • Plasmids / genetics
  • Plasmids / pharmacokinetics
  • Plasmids / therapeutic use*
  • Polyethyleneimine / chemistry
  • RNA, Small Interfering / genetics*

Substances

  • CD146 Antigen
  • Magnetite Nanoparticles
  • Mcam protein, mouse
  • RNA, Small Interfering
  • Polyethyleneimine
  • DNA