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Investigation of siRNA-Loaded Polyethylenimine-Coated Human Serum Albumin Nanoparticle Complexes for the Treatment of Breast Cancer

机译:载有siRNA的聚乙烯亚胺涂层人血清白蛋白纳米粒子复合物治疗乳腺癌的研究。

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摘要

Small interfering RNA (siRNA) molecules have great potential for developing into a future therapy for breast cancer. To overcome the issues related to rapid degradation and low transfection of naked siRNA, polyethylenimine (PEI)-coated human serum albumin (HSA) nanoparticles have been characterized and studied here for efficient siRNA delivery to the MCF-7 breast cancer cell line. The optimized nanoparticles were ~90 nm in size, carrying a surface charge of +26 mV and a polydispersity index (PDI) less than 0.25. The shape and morphology of the particles was studied using electron microscopy. A cytotoxicity assessment of the nanoparticles showed no correlation of cytotoxicity with HSA concentration, while using high molecular weight PEI (MW of 70 against 25 kDa) showed higher cytotoxicity. The optimal transfection achieved of fluorescin-tagged siRNA loaded into PEI-coated HSA nanoparticles was 61.66 ± 6.8%, prepared with 6.25 μg of PEI (25 kDa) added per mg of HSA and 20 mg/ml HSA, indicating that this nonviral vector may serve as a promising gene delivery system.
机译:小分子干扰RNA(siRNA)分子具有巨大的潜力,可以发展成为乳腺癌的未来疗法。为了克服与裸siRNA的快速降解和低转染有关的问题,已对聚乙烯亚胺(PEI)包被的人血清白蛋白(HSA)纳米颗粒进行了表征,并在此进行了研究,以将siRNA有效递送至MCF-7乳腺癌细胞系。优化的纳米粒子尺寸约为90 nm,表面电荷+26 mV,多分散指数(PDI)小于0.25。使用电子显微镜研究了颗粒的形状和形态。纳米颗粒的细胞毒性评估显示细胞毒性与HSA浓度没有相关性,而使用高分子量PEI(分子量为70相对于25 kDa的分子量)显示出更高的细胞毒性。加载有PEI涂层的HSA纳米颗粒中的荧光素标记siRNA的最佳转染效果为61.66±6.8%,每mg HSA和20 mg / ml HSA添加6.25μgPEI(25 kDa),表明该非病毒载体可能作为有前途的基因传递系统。

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