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Aggregation-induced emission (AIE) dye loaded polymer nanoparticles for gene silencing in pancreatic cancer and their in vitro and in vivo biocompatibility evaluation

机译:用于胰腺癌基因沉默的聚集诱导发射(AIE)染料聚合物纳米颗粒及其体外和体内生物相容性评估

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摘要

We have developed aggregation-induced emission (AIE) dye loaded polymer nanoparticles with deep-red emission for siRNA delivery to pancreatic cancer cells. Two US Food and Drug Administration (FDA) approved surfactant polymers, Pluronics F127 and PEGylated phospholipid, were used to prepare the dye-loaded nanoparticle formulations and they can be used as nanovectors for gene silencing of mutant K-ras in pancreatic cancer cells. The successful transfection of siRNA by the developed nanovectors was confirmed by the fluorescent imaging and quantified through flow cytometry. Quantitative real time polymerase chain reaction (PCR) indicates that the expression of the mutant K-ras oncogene from the MiaPaCa-2 pancreatic cancer cells has been successfully suppressed. More importantly, our in vivo toxicity study has revealed that both the nanoparticle formulations are highly biocompatible in BALC/c mice. Overall, our results suggest that the AIE dye-loaded polymer nanoparticle formulations developed here are suitable for gene delivery and have high potential applications in translational medicine research.
机译:我们已经开发了具有深红色发射的聚集诱导发射(AIE)染料负载聚合物纳米颗粒,用于将siRNA传递至胰腺癌细胞。两种美国食品药品监督管理局(FDA)批准的表面活性剂聚合物Pluronics F127和PEG化磷脂用于制备负载染料的纳米颗粒制剂,它们可用作纳米载体,用于沉默胰腺癌细胞中突变K-ras的基因。已开发的纳米载体成功转染了siRNA,通过荧光成像进行了证实,并通过流式细胞仪进行了定量。实时定量聚合酶链反应(PCR)表明,来自MiaPaCa-2胰腺癌细胞的突变K-ras癌基因的表达已被成功抑制。更重要的是,我们的体内毒性研究表明,两种纳米颗粒制剂在BALC / c小鼠中都具有高度的生物相容性。总体而言,我们的结果表明,此处开发的AIE染料负载的聚合物纳米粒子制剂适合用于基因传递,并且在转化医学研究中具有很高的应用潜力。

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