Surface functionalisation of PLGA nanoparticles for gene silencing
Surface functionalisation of PLGA nanoparticles for gene silencing
复制标题
DOI：
10.1016/j.biomaterials.2010.03.069
复制
发表时间：
2010-07-01
期刊：
影响因子：
14
通讯作者：
Howard, Kenneth A.
中科院分区：
文献类型：
--
作者：
Andersen, Morten O.;Lichawska, Agata;Howard, Kenneth A.
这项工作提出了一种方法，用于装饰聚（丙交酯-共-乙交酯）（PLGA）纳米粒子的表面与聚乙烯亚胺（PEI）利用鲸蜡基衍生物，以改善表面功能化和siRNA的交付。亚微米粒子是通过使用苯甲醇的乳液扩散法制备的。我们通过X射线光电子能谱（XPS）证明，与非十六烷基化PEI制剂相比，使用十六烷基衍生物的胺的表面呈现高2.6倍（分别为6.5%和2.5%表面氮）。通过光谱学、荧光显微镜和流式细胞术显示修饰的颗粒结合并介导siRNA递送到人骨肉瘤细胞系U2 OS和鼠巨噬细胞系J774.1中。用含有十六烷基化PEI的颗粒实现了U2 OS细胞中抗凋亡癌基因BCL-w的特异性降低（53%），而没有细胞毒性。此外，含有十六烷基化PEI的颗粒在J774.1细胞中实现了64%的TNF α沉默。这种快速的表面改性的PLGA纳米粒子的方法，促进其应用替代十六烷基功能衍生物作为一种策略，以控制特定的纳米粒子的生物学特性。(c)2010爱思唯尔有限公司版权所有。
This work presents a method for decorating the surface of poly (lactide-co-glycolide) (PLGA) nanoparticles with polyethyleneimine (PEI) utilising a cetyl derivative to improve surface functionalisation and siRNA delivery. Sub-micron particles were produced by an emulsion-diffusion method using benzyl alcohol. We demonstrate by x-ray photoelectron spectroscopy (XPS), 2.6 times higher surface presentation of amines using the cetyl derivative compared to non-cetylated-PEI formulations (6.5 and 2.5% surface nitrogen, respectively). The modified particles were shown by spectroscopy, fluorescent microscopy and flow cytometry to bind and mediate siRNA delivery into the human osteosarcoma cell line U2OS and the murine macrophage cell line J774.1. Specific reduction in the anti-apoptotic oncogene BCL-w in U2OS cells was achieved with particles containing cetylated-PEI (53%) with no cellular, toxicity. In addition, particles containing cetylated-PEI achieved 64% silencing of TNF alpha in J774.1 cells. This rapid method for surface modification of PLGA nanoparticles promotes its application for alternative cetylated functional derivatives as a strategy to control specific biological properties of nanoparticles. (c) 2010 Elsevier Ltd. All rights reserved.