Microdistribution of MC1R-targeted polyplexes in murine melanoma tumor tissue

Biomaterials. 2013 Dec;34(38):10209-16. doi: 10.1016/j.biomaterials.2013.08.076. Epub 2013 Sep 27.


Targeted sodium-iodide symporter (NIS) gene transfer can be considered as a promising approach for diagnostics of specific types of cancer. For this purpose we used targeted polyplexes based on PEI-PEG-MC1SP block-copolymer containing MC1SP-peptide, a ligand specific for melanocortin receptor-1 (MC1R) overexpressed on melanoma cells. Targeted polyplexes demonstrated enhanced NIS gene transfer compared to non-targeted (lacking MC1SP) ones in vitro. Using dorsal skinfold chamber and intravital microscopy we evaluated accumulation and microdistribution of quantum dot-labeled polyplexes in tumor and normal subcutaneous tissues up to 4 h after intravenous injection. Polyplexes demonstrated significantly higher total accumulation in tumor tissue in comparison with subcutaneous ones (control). Targeted and non-targeted polyplexes extravasated and penetrated into the tumor tissue up to 20 μm from the vessel walls. In contrast, in normal subcutaneous tissue polyplexes penetrated not more than 3 μm from the vessel walls with the level of extravasated polyplexes 400-fold less than in tumor. Accumulated polyplexes in tumor tissue caused NIS gene expression. Subsequent (123)I(-) intravenous injection resulted in 6.8 ± 1.1 and 4.5 ± 0.8% ID/g (p < 0.001) iodide accumulation in tumors in the case of targeted and non-targeted polyplexes, respectively, as was shown using SPECT/CT.

Keywords: Block-copolymer; Confocal microscopy; Intratumoral distribution; Nanoparticles; Targeted gene transfer; Tumor diagnostics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Gene Transfer Techniques
  • Melanoma / metabolism*
  • Melanoma / therapy
  • Mice
  • Microscopy, Confocal
  • Nanoparticles / chemistry*
  • Polymers / chemistry*
  • Receptor, Melanocortin, Type 1 / genetics
  • Receptor, Melanocortin, Type 1 / metabolism*


  • Polymers
  • Receptor, Melanocortin, Type 1