期刊
BIOMATERIALS
卷 34, 期 38, 页码 10209-10216出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2013.08.076
关键词
Block-copolymer; Nanoparticles; Targeted gene transfer; Confocal microscopy; Intratumoral distribution; Tumor diagnostics
资金
- Russian Federation State [16.512.12.2002, 13411.100.8799.13.135, 11411.1008700.13.084]
- Russian Foundation for Basic Research [13-04-01282-a]
- NIH [P50 NS20023]
- M.V. Lomonosov Moscow State University Program of Development
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 gm from the vessel walls. In contrast, in normal subcutaneous tissue polyplexes penetrated not more than 3 p.m 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 I-123(-) 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. (C) 2013 Elsevier Ltd. All rights reserved.
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