Department of Pharmaceutics, National Institute of Pharmaceutical Education & Research (NIPER), Hyderabad, India.
Laboratoire de Chimie de Coordination du CNRS (LCC), Toulouse, France.
J Biomed Mater Res A. 2019 Sep;107(9):1933-1944. doi: 10.1002/jbm.a.36701. Epub 2019 Apr 29.
Irresponsiveness of triple negative breast cancer (TNBC) toward conventional therapies has drawn attention toward siRNA therapeutics. In gene delivery, dendrimers are gaining significant attention due to their characteristic features and polo-like kinase (PLK1) is reported as a potential target for TNBC. In this work, phosphorus and polyamidoamine dendrimer (generation 3 and 4 of each type) are explored to address delivery challenges of PLK1 siRNA (siPLK1). Dendriplexes were formed and complexation was found at 3:1 N/P ratio for all dendrimers by gel electrophoresis. Complexation was also supported by zeta potential, circular dichroism and intercalation assay. Dendriplexes were found to be stable in presence of ribonuclease and serum. Dendriplexes resulted in enhanced cell uptake of siPLK1 compared to siPLK1 solution in MDA-MB-231 and MCF-7 cells. Dendriplexes caused increased cell arrest in sub-G1 phase compared to solution. These observations suggested phosphorus and polyamidoamine dendrimers as potential carriers for siPLK1 delivery to treat TNBC.
三阴性乳腺癌（TNBC）对常规疗法的不响应引起了人们对 siRNA 治疗的关注。在基因传递中，由于树状聚合物具有特征性，因此引起了人们的关注，并且有报道称丝氨酸/苏氨酸激酶（PLK1）是 TNBC 的潜在靶标。在这项工作中，探索了磷和聚酰胺胺树状聚合物（每种类型的第 3 代和第 4 代），以解决 PLK1 siRNA（siPLK1）的传递挑战。通过凝胶电泳发现，所有树状聚合物在 3:1 的 N/P 比下形成了树状聚合物，并发生了复合物形成。通过 zeta 电位、圆二色性和嵌入测定也支持了复合物的形成。在存在核糖核酸酶和血清的情况下，树状聚合物复合物是稳定的。与 siPLK1 溶液相比，树状聚合物复合物使 MDA-MB-231 和 MCF-7 细胞中 siPLK1 的细胞摄取增加。与溶液相比，树状聚合物复合物使细胞在 sub-G1 期的阻滞增加。这些观察结果表明，磷和聚酰胺胺树状聚合物是将 siPLK1 递送至治疗 TNBC 的潜在载体。
