Poly-L-lysine Functionalized Large Pore Cubic Mesostructured Silica Nanoparticles as Biocompatible Carriers for Gene Delivery
Poly-L-lysine Functionalized Large Pore Cubic Mesostructured Silica Nanoparticles as Biocompatible Carriers for Gene Delivery
复制标题
DOI：
10.1021/nn2039643
复制
发表时间：
2012-03-01
期刊：
影响因子：
17.1
通讯作者：
Qiao, Shi Zhang
中科院分区：
文献类型：
--
作者：
Hartono, Sandy B.;Gu, Wenyi;Qiao, Shi Zhang
设计了一种新型基因载体材料--L赖氨酸修饰的大孔介孔二氧化硅纳米颗粒。合成的LP-MSN的直径为100-200 nm，由立方介观结构的笼状孔组成。腔的大小约为28 nm，入射尺寸为13.4 nm。X射线光电子能谱、固态C-13魔角旋转核磁共振、傅里叶变换红外光谱和热重分析证实了共价固定化成功地将PLL接枝到二氧化硅表面。与天然未修饰的二氧化硅颗粒相比，经PLL修饰的纳米颗粒对寡聚DNA的结合能力显著提高。因此，PLL功能化的纳米颗粒显示出很强的向Hela细胞运送寡聚DNA-Cy3(siRNA的模型)的能力。此外，与氨基功能化纳米粒和天然纳米粒相比，PLL功能化纳米粒作为基因载体具有更好的性能。该系统被测试为在骨肉瘤癌细胞中传递针对小型脑相关激酶和Polo-like kinase1的功能性siRNA。在这里，功能化的颗粒显示出巨大的潜力，可以有效地将基因转移到癌细胞中，因为诱导骨肉瘤癌细胞的细胞活力下降。此外，PLL修饰的二氧化硅纳米颗粒还具有很高的生物相容性，低细胞毒性可达100微克/毫升。
Large pore mesoporous silica nanoparticles (LP-MSNs) functionalized with poly-L-lysine (PLL) were designed as a new carrier material for gene delivery applications. The synthesized LP-MSNs are 100-200 nm in diameter and are composed of cage-like pores organized in a cubic mesostructure. The size of the cavities is about 28 nm with an entrance size of 13.4 nm. Successful grafting of PLL onto the silica surface through covalent immobilization was confirmed by X-ray photoelectron spectroscopy, solid-state C-13 magic-angle spinning nuclear magnetic resonance, Fourier transformed infrared, and thermogravimetric analysis. As a result of the particle modification with PLL, a significant increase of the nanoparticle binding capacity for oligo-DNAs was observed compared to the native unmodified silica particles. Consequently, PLL-functionalized nanoparticles exhibited a strong ability to deliver oligo DNA-Cy3 (a model for siRNA) to Hela cells. Furthermore, PLL-functionalized nanoparticles were proven to be superior as gene carriers compared to amino-functionalized nanoparticles and the native nanoparticles. The system was tested to deliver functional siRNA against minibrain-related kinase and polo-like kinase 1 in osteosarcoma cancer cells. Here, the functionalized particles demonstrated great potential for efficient gene transfer into cancer cells as a decrease of the cellular viability of the osteosarcoma cancer cells was induced. Moreover, the PLL-modified silica nanoparticles also exhibit a high biocompatibility, with low cytotoxicity observed up to 100 mu g/mL.