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Design and preparation of a new multi-targeted drug delivery system using multifunctional nanoparticles for co-delivery of siRNA and paclitaxel
Journal of Pharmaceutical Analysis ( IF 6.1 ) Pub Date : 2020-04-23 , DOI: 10.1016/j.jpha.2020.04.005
Sara Hosayni Nasab 1 , Amin Amani 1, 2 , Hossein Ali Ebrahimi 3 , Ali Asghar Hamidi 4
Affiliation  

Drug resistance is a great challenge in cancer therapy using chemotherapeutic agents. Administration of these drugs with siRNA is an efficacious strategy in this battle. Here, the present study tried to incorporate siRNA and paclitaxel (PTX) simultaneously into a novel nanocarrier. The selectivity of carrier to target cancer tissues was optimized through conjugation of folic acid (FA) and glucose (Glu) onto its surface. The structure of nanocarrier was formed from ternary magnetic copolymers based on FeCo-polyethyleneimine (FeCo-PEI) nanoparticles and polylactic acid-polyethylene glycol (PLA-PEG) gene delivery system. Biocompatibility of FeCo-PEI-PLA-PEG-FA(NPsA), FeCo-PEI-PLA-PEG-Glu (NPsB) and FeCo-PEI-PLA-PEG-FA/Glu (NPsAB) nanoparticles and also influence of PTX-loaded nanoparticles on in vitro cytotoxicity were examined using MTT assay. Besides, siRNA-FAM internalization was investigated by fluorescence microscopy. The results showed the blank nanoparticles were significantly less cytotoxic at various concentrations. Meanwhile, siRNA-FAM/PTX encapsulated nanoparticles exhibited significant anticancer activity against MCF-7 and BT-474 cell lines. NPsAB/siRNA/PTX nanoparticles showed greater effects on MCF-7 and BT-474 cells viability than NPsA/siRNA/PTX and NPsB/siRNA/PTX. Also, they induced significantly higher anticancer effects on cancer cells compared with NPsA/siRNA/PTX and NPsB/siRNA/PTX due to their multi-targeted properties using FA and Glu. We concluded that NPsAB nanoparticles have a great potential for co-delivery of both drugs and genes for use in gene therapy and chemotherapy.



中文翻译:


设计和制备新型多靶点药物递送系统,使用多功能纳米粒子共同递送siRNA和紫杉醇



耐药性是使用化疗药物进行癌症治疗的一个巨大挑战。将这些药物与 siRNA 一起施用是这场战斗中的有效策略。本研究尝试将 siRNA 和紫杉醇 (PTX) 同时整合到新型纳米载体中。通过将叶酸(FA)和葡萄糖(Glu)结合到其表面,优化了载体对靶癌组织的选择性。纳米载体的结构由基于FeCo-聚乙烯亚胺(FeCo-PEI)纳米粒子和聚乳酸-聚乙二醇(PLA-PEG)基因传递系统的三元磁性共聚物形成。 FeCo-PEI-PLA-PEG-FA(NPsA)、FeCo-PEI-PLA-PEG-Glu (NPsB) 和 FeCo-PEI-PLA-PEG-FA/Glu (NPsAB) 纳米颗粒的生物相容性以及 PTX 负载的影响采用MTT法检测纳米粒子的体外细胞毒性。此外,通过荧光显微镜研究了siRNA-FAM内化。结果显示空白纳米颗粒在不同浓度下的细胞毒性显着降低。同时,siRNA-FAM/PTX封装的纳米颗粒对MCF-7和BT-474细胞系表现出显着的抗癌活性。 NPsAB/siRNA/PTX 纳米颗粒对 MCF-7 和 BT-474 细胞活力的影响比 NPsA/siRNA/PTX 和 NPsB/siRNA/PTX 更大。此外,由于使用 FA 和 Glu 的多靶点特性,与 NPsA/siRNA/PTX 和 NPsB/siRNA/PTX 相比,它们对癌细胞具有显着更高的抗癌作用。我们得出的结论是,NPsAB 纳米颗粒在药物和基因共同递送方面具有巨大的潜力,可用于基因治疗和化疗。

更新日期:2020-04-23
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