Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska St., Lodz 90-236, Poland.
Molecules. 2013 Apr 15;18(4):4451-66. doi: 10.3390/molecules18044451.
There are many types of dendrimers used as nanomolecules for gene delivery but there is still an ongoing search for ones that are able to effectively deliver drugs to cells. The possibility of gene silencing using siRNA gives hope for effective treatment of numerous diseases. The aim of this work was to investigate in vitro biophysical properties of dendriplexes formed by siRNA and cationic phosphorus dendrimers of 3rd and 4th generation. First, using the ethidium bromide intercalation method, it was examined whether dendrimers have an ability to form complexes with siRNA. Next, the characterisation of dendriplexes formed at different molar ratios was carried out using biophysical methods. The effects of zeta potential, size and changes of siRNA conformation on the complexation with dendrimers were examined. It was found that both phosphorus dendrimers interacted with siRNA. The zeta potential values of dendriplexes ranged from negative to positive and the hydrodynamic diameter depended on the number of dendrimer molecules in the complex. Furthermore, using circular dichroism spectroscopy it was found that cationic phosphorus dendrimers changed only slightly the shape of siRNA CD spectra, thus they did not induce significant changes in the nucleic acid secondary structure during complex formation.
有许多类型的树枝状聚合物被用作基因传递的纳米分子，但人们仍在寻找能够将药物有效递送到细胞的树枝状聚合物。使用 siRNA 进行基因沉默的可能性为许多疾病的有效治疗带来了希望。本工作的目的是研究由 siRNA 和第三代和第四代阳离子磷树枝状聚合物形成的树枝状聚合物的体外生物物理性质。首先，通过溴化乙锭嵌入法，检查树枝状聚合物是否具有与 siRNA 形成复合物的能力。接下来，使用生物物理方法对不同摩尔比形成的树枝状聚合物进行了表征。研究了zeta 电位、大小和 siRNA 构象变化对与树枝状聚合物复合的影响。结果发现，两种磷树枝状聚合物都与 siRNA 相互作用。树枝状聚合物的 zeta 电位值从负到正变化，水动力直径取决于复合物中树枝状聚合物分子的数量。此外，通过圆二色性光谱发现，阳离子磷树枝状聚合物仅略微改变 siRNA 的 CD 光谱形状，因此在形成复合物过程中不会引起核酸二级结构的显著变化。
