An investigation of the effects of nanosize delivery system for antisense oligonucleotide on esophageal squamous cancer cells.

Telomerase is an RNA-dependent DNA polymerase that synthesizes telomeric DNA sequences, which provide tandem GT-rich repeats (TTAGGG)n to compensate telomere shortening and play an important role in cellular aging and carcinogenesis.(1) Recent studies demonstrated that telomerase activity is absent in most normal human somatic cells but present in over 90% of tumor cells and immortalized cells. Human telomerase reverse transcriptase (hTERT) is the rate-limiting factor of telomerase activity and also ASODN (antisense oligodeoxynucleotides) targeting to hTERT gene represent a promising approach to tumor therapy. However, the use of ASODN is determined by combination of biological stability, successful uptake into the targeted cells, resistance to nucleases and so forth. To satisfy these conditions, the key is to establish proper delivery system to carry and protect ASODN. Accumulating data have revealed that polyethylenimine (PEI) with numerous positive charges is one of the most effective DNA-delivery systems in vitro and in vivo due to its polycationic property and proton sponge mechanism, however, it lacks the function of targeting to tumor cells. Recently, some studies indicated that coupling special ligand like NGR (N: asparagine, G: glycine, R: arginine) peptide targeting to tumor blood vessels with delivery system can enhance the efficacy of gene transfection. The purpose of this study was to investigate the effects of nanosize delivery system for antisense oligonucleotide for hTERT in vitro on EC9706 cells and in vivo on tumor tissue.