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

Microdistribution of MC1R-targeted polyplexes in murine melanoma tumor tissue.

Author information

1
Laboratory of Molecular Genetics of Intracellular Transport, Institute of Gene Biology, Russian Academy of Sciences, 34/5, Vavilov St., 119334 Moscow, Russia; Department of Biophysics, Faculty of Biology, Moscow State University, 1-12, Leninskie Gory, 119991 Moscow, Russia. Electronic address: mdurymanov@gmail.com.

Abstract

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

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