Ionov Maksim, Lazniewska Joanna, Dzmitruk Volha, Halets Inessa, Loznikova Svetlana, Novopashina Darya, Apartsin Evgeny, Krasheninina Olga, Venyaminova Alya, Milowska Katarzyna, Nowacka Olga, Gomez-Ramirez Rafael, de la Mata Francisco Javier, Majoral Jean-Pierre, Shcharbin Dzmitry, Bryszewska Maria
Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Poland.
Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Poland.
Int J Pharm. 2015 May 15;485(1-2):261-9. doi: 10.1016/j.ijpharm.2015.03.024. Epub 2015 Mar 16.
This paper examines a perspective on the use of newly engineered nanomaterials as effective and safe carriers of genes for the therapy of cancer. Three different groups of cationic dendrimers (PAMAM, phosphorus and carbosilane) were complexed with anticancer siRNA and their biophysical properties of the dendriplexes analyzed. The potential of the dendrimers as nanocarriers for anticancer siBcl-xl, siBcl-2, siMcl-1 siRNAs and a siScrambled sequence was explored. Dendrimer/siRNA complexes were characterized by methods including fluorescence, zeta potential, dynamic light scattering, circular dichroism, gel electrophoresis and transmission electron microscopy. Some of the experiments were done with heparin to check if siRNA can be easily disassociated from the complexes, and whether released siRNA maintains its structure after interaction with the dendrimer. The results indicate that siRNAs form complexes with all the dendrimers tested. Oligoribonucleotide duplexes can be released from dendriplexes after heparin treatment and the structure of siRNA is maintained in the case of PAMAM or carbosilane dendrimers. The dendrimers were also effective in protecting siRNA from RNase A activity. The selection of the best siRNA carrier will be made based on cell culture studies (Part B).
本文探讨了一种关于使用新工程化纳米材料作为治疗癌症的有效且安全的基因载体的观点。将三种不同的阳离子树枝状大分子（聚酰胺-胺、磷和碳硅烷）与抗癌小干扰RNA（siRNA）复合，并分析了树枝状复合物的生物物理性质。研究了树枝状大分子作为抗癌siBcl-xl、siBcl-2、siMcl-1 siRNA和一个随机序列siRNA纳米载体的潜力。通过荧光、zeta电位、动态光散射、圆二色性、凝胶电泳和透射电子显微镜等方法对树枝状大分子/siRNA复合物进行了表征。部分实验使用肝素进行，以检查siRNA是否能轻易从复合物中解离，以及释放后的siRNA在与树枝状大分子相互作用后是否保持其结构。结果表明，siRNA与所有测试的树枝状大分子形成复合物。肝素处理后，寡核糖核苷酸双链体可从树枝状复合物中释放，且在聚酰胺-胺或碳硅烷树枝状大分子的情况下，siRNA的结构得以保持。树枝状大分子在保护siRNA免受核糖核酸酶A活性影响方面也很有效。最佳siRNA载体的选择将基于细胞培养研究（B部分）。
