Kumar Krishan, Vulugundam Gururaja, Jaiswal Pradeep Kumar, Shyamlal Bharti Rajesh Kumar, Chaudhary Sandeep
Laboratory of Organic and Medicinal Chemistry, Department of Chemistry, Malaviya National Institute of Technology, Jawaharlal Nehru Marg, Jaipur 302017, India.
Department of Bioengineering, University of Illinois at Urbana-Champaign, 502 N. Busey, Urbana, IL 61801, USA.
Bioorg Med Chem Lett. 2017 Sep 15;27(18):4288-4293. doi: 10.1016/j.bmcl.2017.08.037. Epub 2017 Aug 18.
This study reports the simultaneous delivery of EGFP siRNA and the chemotherapeutic drug, doxorubicin by means of the composition that results from the electrostatic interaction between positively charged siRNA-complexes of gold nanoparticles (AuNPs) capped with PEI, 25kDa (P25-AuNPs) and negatively charged carboxymethyl cellulose formulated PLGA nanoparticles loaded with doxorubicin. The nanoparticles and their facile interaction were studied by means of dynamic light scattering (DLS), zeta potential, transmission electron microscopic (TEM) measurements. The flow cytometric and confocal microscopic analysis evidenced the simultaneous internalization of both labelled siRNA and doxorubin into around 55% of the HeLa cancer cell population. Fluorescence microscopic studies enabled the visual analysis of EGFP expressing HeLa cells which suggested that the composition mediated codelivery resulted in a substantial downregulation of EGFP expression and intracellular accumulation of doxorubicin. Interestingly, codelivery treatment resulted in an increased cellular delivery of doxorubicin when compared to PLGA-DOX alone treatment. On the other hand, the activity of siRNA complexes of PEI-AuNPs was completely retained even when they were part of composition. The results suggest that this formulation can serve as promising tool for delivery applications in combinatorial anticancer therapy.
本研究报道了通过由带正电荷的、用25kDa聚乙烯亚胺（PEI）包覆的金纳米颗粒（AuNPs）的siRNA复合物（P25-AuNPs）与负载阿霉素的带负电荷的羧甲基纤维素配制的聚乳酸-羟基乙酸共聚物（PLGA）纳米颗粒之间的静电相互作用所形成的组合物，实现增强绿色荧光蛋白（EGFP）siRNA与化疗药物阿霉素的同时递送。通过动态光散射（DLS）、zeta电位、透射电子显微镜（TEM）测量对纳米颗粒及其简便的相互作用进行了研究。流式细胞术和共聚焦显微镜分析证明，标记的siRNA和阿霉素同时内化到约55%的HeLa癌细胞群体中。荧光显微镜研究能够对表达EGFP的HeLa细胞进行可视化分析，这表明该组合物介导的共递送导致EGFP表达的显著下调和阿霉素的细胞内积累。有趣的是，与单独的PLGA-阿霉素治疗相比，共递送治疗导致阿霉素的细胞递送增加。另一方面，即使PEI-AuNPs的siRNA复合物是组合物的一部分，其活性也能完全保留。结果表明，该制剂可作为组合抗癌治疗中递送应用的有前景的工具。
