An investigation of the effects of nanosize delivery system for antisense oligonucleotide on esophageal squamous cancer cells
An investigation of the effects of nanosize delivery system for antisense oligonucleotide on esophageal squamous cancer cells
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DOI：
10.4161/cbt.7.11.6879
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发表时间：
2008-11-01
影响因子：
3.6
通讯作者：
Zhang, Zhenzhong
中科院分区：
文献类型：
--
作者：
Li, Huixiang;Wang, Jin;Zhang, Zhenzhong
端粒酶是一种RNA依赖的DNA聚合酶，它合成端粒DNA序列，提供富含GT的串联重复序列（TTAGGG）n来补偿端粒缩短，在细胞衰老和癌变中起重要作用。(1)最近的研究表明，端粒酶活性在大多数正常人的体细胞中不存在，但在90%以上的肿瘤细胞和永生化细胞中存在。人端粒酶逆转录酶（Human telomerase reverse transcriptase，hTERT）是端粒酶活性的限速因子，针对hTERT基因的反义寡核苷酸（antisense oligodeoxynucleotides，ASODN）是一种很有前途的肿瘤治疗方法。（2，3）然而，ASODN的使用取决于生物稳定性、成功摄取到靶细胞中、对核酸酶的抗性等的组合。(4)要满足这些条件，关键是要建立合适的载体系统来承载和保护ASODN。聚乙烯亚胺（polyethylenimine，PEI）由于其多阳离子性和质子海绵机制，是体内外最有效的DNA载体之一，但缺乏靶向肿瘤细胞的功能。近年来，有研究表明，将靶向肿瘤血管的NGR（N：天冬酰胺，G：甘氨酸，R：精氨酸）肽等特异性配体与递送系统偶联，可以提高基因转染的效率。（5-8）本研究的目的是研究用于hTERT反义颗粒的纳米尺寸递送系统在体外对EC 9706细胞和在体内对肿瘤组织的影响。
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.(2,3) However, the use of ASODN is determined by combination of biological stability, successful uptake into the targeted cells, resistance to nucleases and so forth.(4) 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.(5-8)The purpose of this study was to investigate the effects of nanosize delivery system for antisense oligonucleoticle for hTERT in vitro on EC9706 cells and in vivo on tumor tissue.