Hemmati Mohammad, Kazemi Bahram, Najafi Farhood, Zarebkohan Amir, Shirkoohi Reza
a Medical Physics and Biomedical Engineering and Nanomedicine Department, Faculty of Medicine, Shahid Beheshti Medical University , Tehran , Iran .
b Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences , Tehran , Iran .
J Drug Target. 2016;24(5):408-21. doi: 10.3109/1061186X.2015.1078338. Epub 2015 Sep 4.
Hyperbranched poly(amidoamine) (HPAMAM), structurally analogous to polyamidoamine dendrimer (PAMAM) dendrimers, has been suggested to be an effective carrier for gene delivery. In the present study, glutamic acid-modified hPAMAM was developed as a novel non-viral gene carrier for the first time. The hPAMAM was synthesized by using a modified one-pot method. DNA was found to be bound to hPAMAM at different weight ratios (WhPAMAM/WDNA). The resulting HPAMAM-Glu20 was able to efficiently protect the encapsulated-DNA against degradation for over 2 h. In addition to low cytotoxicity, the transfection efficiency of hPAMAM-Glu20 represented much higher (p < 0.05) than that of Lipofectamine 2000 in both MCF7 and MDA-MB231 cells. Cellular uptake of the hPAMAM-Glu20 in MDA-MB231 cells, 173.56 ± 1.37%, was significantly higher than that of MCF7 cells, 65.00 ± 1.73% (p < 0.05). The results indicated that hPAMAM-Glu20-mediated gene delivery to breast cancer cells is a feasible and effective strategy that may provide a new therapeutic avenue as a non-viral gene delivery carrier. In addition, it was found that hPAMAM-glutamic amino acid (Glu)-based gene delivery is an economical, effective and biocompatible method.
超支化聚（酰胺胺）（HPAMAM）在结构上与聚酰胺胺树枝状大分子（PAMAM）类似，已被认为是一种有效的基因递送载体。在本研究中，首次开发了谷氨酸修饰的hPAMAM作为新型非病毒基因载体。hPAMAM采用改良的一锅法合成。发现DNA以不同的重量比（WhPAMAM/WDNA）与hPAMAM结合。所得的HPAMAM-Glu20能够有效保护包裹的DNA在2小时以上不被降解。除了低细胞毒性外，hPAMAM-Glu20在MCF7和MDA-MB231细胞中的转染效率均比Lipofectamine 2000高得多（p < 0.05）。hPAMAM-Glu20在MDA-MB231细胞中的细胞摄取率为173.56±1.37%，显著高于MCF7细胞的65.00±1.73%（p < 0.05）。结果表明，hPAMAM-Glu20介导的基因递送至乳腺癌细胞是一种可行且有效的策略，可能作为非病毒基因递送载体提供一种新的治疗途径。此外，发现基于hPAMAM-谷氨酸（Glu）的基因递送是一种经济、有效且生物相容的方法。
