A gold nanoparticle platform for the delivery of functional microRNAs into cancer cells
A gold nanoparticle platform for the delivery of functional microRNAs into cancer cells
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DOI：
10.1016/j.biomaterials.2012.10.023
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发表时间：
2013-01-01
期刊：
影响因子：
14
通讯作者：
Gunaratne, Preethi H.
中科院分区：
文献类型：
--
作者：
Ghosh, Rajib;Singh, Lalithya C.;Gunaratne, Preethi H.
缺乏可负担得起的技术来大规模地将microRNA和siRNA递送到细胞中，这阻碍了我们快速解析数百个失调基因/microRNA以识别复杂疾病的驱动因素的努力。裸microRNA的不稳定性和聚阴离子性质阻碍了有效的细胞摄取并缩短了半衰期。病毒递送需要克隆，微小RNA模拟物/抑制剂需要昂贵的修饰，并且两者都需要毒性脂质转染或电穿孔。为了解决这些挑战，我们开发了一种稳健的方法，用于将未修饰的microRNA递送到半胱胺功能化的金纳米颗粒（AuNP）上的细胞中。我们在两种不同的肿瘤模型中验证了我们的方法，并发现miR（1）-AuNP 10-S-PEG的最佳配方（0.5）具有最高的有效载荷（比脂质体转染高10-20倍），毒性最低（处理后98%的细胞活力），有效摄取（96%的细胞服用了它），最快的内体逃逸和增加的半衰期（至少5天）影响细胞增殖和靶基因表达模式。(c)2012爱思唯尔有限公司保留所有权利。
Lack of affordable technologies for delivering microRNAs and siRNAs into cells on a large scale has hindered our efforts to rapidly parse through hundreds of dysregulated genes/microRNAs in order to identify drivers of complex diseases. The instability and polyanionic nature of naked microRNAs impede efficient cellular uptake and reduce half-life. Viral delivery requires cloning, microRNA mimics/inhibitors require costly modifications, and both require toxic lipofection or electroporation. To address these challenges, we developed a robust method for delivering unmodified microRNAs into cells on cysteamine-functionalized gold nanoparticles (AuNPs). We validated our method in two different tumor models and found that the best formulation of miR(1)-AuNP10-S-PEG(0.5) had the highest payload (10-20 fold higher than lipofection), lowest toxicity (98% of cell viability following treatment), efficient uptake (96% of cells took it), fastest endosomal escape and increased half-lives (at least 5 days) impacting cell proliferation and patterns of target gene expression. (c) 2012 Elsevier Ltd. All rights reserved.