Liu Lanxia, Wang Hai, Liu Qi, Duan Mingli, Dong Xia, Zhu Dunwan, Zhu Yingjun, Leng Xigang
Lab of Bioengineering, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Biomedical Materials, Tianjin, 300192, China.
Department of Gynecology, Tianjin Central Hospital of Gynecology Obstetrics, Tianjin, 300100, China.
J Biomed Mater Res A. 2016 Oct;104(10):2394-400. doi: 10.1002/jbm.a.35775. Epub 2016 May 25.
Hepatocellular carcinoma (HCC) is the fifth most prevalent malignancy and the third leading cause of cancer-related deaths worldwide. More effective cures for HCC patients are urgently needed, of which gene therapy is among those with the most potential. We previously developed a novel gene carrier by conjugating low molecular weight chitosan with TAT (transactivator of transcription) peptide and LHRH (luteinizing hormone-releasing hormone) analog, with the resultant TAT-LHRH-chitosan conjugate (TLC) demonstrating high selectivity for hepatoma cells in vitro. However, it remains unclear whether TLC can deliver the genes to the target organs and tissues in vivo, which is one of the critical features determining their medical application potential. The current study further investigated the in vivo distribution of TLC/DNA nanoparticles (TLCDNPs) in the nude mice with subcutaneous hepatoma xenografts. It was found that TLCDNPs delayed the renal clearance of DNA and prolonged its circulation time as compared with CS/DNA complexes (CDNPs) and naked DNA, but failed to demonstrate enhanced accumulation of DNA in the hepatoma xenografts. The mechanisms regarding the failure of TLCDNPs' tumor targeting in the mice bearing subcutaneous hepatoma xenografts remain unclear and need to be further addressed. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2394-2400, 2016.
肝细胞癌（HCC）是全球第五大常见恶性肿瘤，也是癌症相关死亡的第三大主要原因。迫切需要为HCC患者找到更有效的治疗方法，基因治疗是其中最具潜力的方法之一。我们之前通过将低分子量壳聚糖与TAT（转录激活因子）肽和LHRH（促黄体生成素释放激素）类似物偶联，开发了一种新型基因载体，所得的TAT-LHRH-壳聚糖偶联物（TLC）在体外对肝癌细胞表现出高选择性。然而，TLC是否能在体内将基因递送至靶器官和组织仍不清楚，而这是决定其医学应用潜力的关键特征之一。当前研究进一步考察了TLC/DNA纳米颗粒（TLCDNPs）在皮下肝癌异种移植裸鼠体内的分布情况。结果发现，与CS/DNA复合物（CDNPs）和裸DNA相比，TLCDNPs延缓了DNA的肾脏清除并延长了其循环时间，但未能在肝癌异种移植瘤中显示出DNA的蓄积增强。TLCDNPs在皮下肝癌异种移植瘤小鼠中肿瘤靶向失败的确切机制尚不清楚，需要进一步研究。© 2016威利期刊公司。《生物医学材料研究杂志》A部分：第104A卷：2394 - 2400页，2016年。
