Key Laboratory of Drug Targeting and Novel Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041, People's Republic of China.
Nanotechnology. 2010 Mar 12;21(10):105106. doi: 10.1088/0957-4484/21/10/105106. Epub 2010 Feb 15.
Recombinant adenovirus (Ad)-mediated gene therapy is an exciting novel strategy in cancer treatment. However, poor infection efficiency with coxsackievirus and adenovirus receptor (CAR) down-regulated cancer cell lines is one of the major challenges for its practical and extensive application. As an alternative method of viral gene delivery, a non-viral carrier using cationic materials could compensate for the limitation of adenovirus. In our study, adenovectors were complexed with a new synthetic polymer PEI-DEG-bis-NPC (PDN) based on polyethylenimine (PEI), and then the properties of the vehicle were characterized by measurement of size distribution, zeta potential and transmission electron microscopy (TEM). Enhancement of gene transduction by Ad/PDN complexes was observed in both CAR-overexpressing cell lines (A549) and CAR-lacking cell lines (MDCK, CHO, LLC), as a result of facilitating binding and cell uptake of adenoviral particles by the cationic component. Ad/PDN complexes also promoted the inhibition of tumor growth in vivo and prolonged the survival time of tumor-bearing mice. These data suggest that a combination of viral and non-viral gene delivery methods may offer a new approach to successful cancer gene therapy.
重组腺病毒（Ad）介导的基因治疗是癌症治疗中令人兴奋的新策略。然而，由于柯萨奇病毒和腺病毒受体（CAR）下调的癌细胞系感染效率低，这是其实际广泛应用的主要挑战之一。作为病毒基因传递的替代方法，使用阳离子材料的非病毒载体可以弥补腺病毒的局限性。在我们的研究中，腺病毒载体与基于聚乙烯亚胺（PEI）的新型合成聚合物 PEI-DEG-bis-NPC（PDN）复合，然后通过测量粒径分布、zeta 电位和透射电子显微镜（TEM）来表征载体的性质。观察到 Ad/PDN 复合物在 CAR 过表达细胞系（A549）和 CAR 缺乏细胞系（MDCK、CHO、LLC）中增强了基因转导，这是由于阳离子成分促进了腺病毒颗粒的结合和细胞摄取。Ad/PDN 复合物还促进了体内肿瘤生长的抑制和荷瘤小鼠存活时间的延长。这些数据表明，病毒和非病毒基因传递方法的结合可能为成功的癌症基因治疗提供新的途径。
