Department of Biomedical Engineering and Artificial Cells and Organs Research Centre, Faculty of Medicine, McGill University, Montreal, QC, Canada.
Cell Biochem Biophys. 2011 Nov;61(2):277-87. doi: 10.1007/s12013-011-9201-9.
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.
小干扰 RNA（siRNA）分子在开发乳腺癌未来疗法方面具有巨大潜力。为了克服裸露 siRNA 快速降解和低转染的问题，本研究中对聚乙烯亚胺（PEI）包覆的人血清白蛋白（HSA）纳米颗粒进行了表征和研究，以有效递送至 MCF-7 乳腺癌细胞系。优化后的纳米颗粒大小约为 90nm，表面电荷为+26mV，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表明，细胞毒性与 HSA 浓度之间没有相关性，而使用高分子量 PEI（MW 为 70 与 25 kDa）则显示出更高的细胞毒性。用荧光素标记的 siRNA 负载到 PEI 包覆的 HSA 纳米颗粒中，实现了最佳转染率为 61.66±6.8%，添加 6.25μg 25kDa 的 PEI 与 20mg/ml HSA 每毫克 HSA 制备，表明这种非病毒载体可能成为一种有前途的基因传递系统。
