Polyethyleneimine coating enhances the cellular uptake of mesoporous silica nanoparticles and allows safe delivery of siRNA and DNA constructs.
Polyethyleneimine coating enhances the cellular uptake of mesoporous silica nanoparticles and allows safe delivery of siRNA and DNA constructs.
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DOI：
10.1021/nn900918w
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发表时间：
2009-10-27
期刊：
影响因子：
17.1
通讯作者：
Nel, Andre E.
中科院分区：
文献类型：
--
作者：
Xia, Tian;Kovochich, Michael;Liong, Monty;Meng, Huan;Kabehie, Sanaz;George, Saji;Zink, Jeffrey I.;Nel, Andre E.
关键词：
表面功能化的介孔二氧化硅纳米粒子（MSNP）可以作为生物活性分子的有效和安全的载体。为了使MSNP成为更有效的递送系统，我们通过增强细胞摄取的官能团修饰了颗粒的表面，并且除了传统的药物递送之外还允许核酸递送。聚乙烯亚胺（PEI）聚合物与表面的非共价连接不仅增加了MSNP细胞摄取，而且产生了DNA和siRNA构建体可以连接的阳离子表面。虽然对于这些核酸的细胞内递送是有效的，但25 KD PEI聚合物不幸地改变了MSNP的安全性特征，否则MSNP是非常安全的。通过试验几种不同的聚合物分子量，可以保持高细胞摄取和转染效率，同时降低甚至消除阳离子MSNP的细胞毒性。用10 KD PEI聚合物包被的颗粒对于用能够敲低GFP表达的siRNA构建体转导HEPA-1细胞特别有效。类似地，GFP质粒的转染在群体中> 70%的细胞中诱导荧光蛋白的有效表达。通过共聚焦显微镜和流式细胞术对这些结果进行定量评估。我们还证明了无毒阳离子MSNP的增强的细胞摄取增强了疏水性抗癌药物紫杉醇向胰腺癌细胞的递送。总之，我们证明，通过仔细选择PEI大小，可以构建能够以最小或没有细胞毒性的核苷酸和增强的药物递送的阳离子MSNP。阳离子MSNP的这种新用途扩展了其治疗用途潜力。
Surface-functionalized mesoporous silica nanoparticles (MSNP) can be used as an efficient and safe carrier for bioactive molecules. In order to make the MSNP a more efficient delivery system, we modified the surface of the particles by a functional group that enhances cellular uptake and allows nucleic acid delivery in addition to traditional drug delivery. Non-covalent attachment of polyethyleneimine (PEI) polymers to the surface not only increases MSNP cellular uptake, but also generates a cationic surface to which DNA and siRNA constructs could be attached. While efficient for intracellular delivery of these nucleic acids, the 25 KD PEI polymer unfortunately changes the safety profile of the MSNP that is otherwise very safe. By experimenting with several different polymer molecular weights, it was possible to retain high cellular uptake and transfection efficiency while reducing or even eliminating cationic MSNP cytotoxicity. The particles coated with the 10 KD PEI polymer was particularly efficient for transducing HEPA-1 cells with a siRNA construct that was capable of knocking down GFP expression. Similarly, transfection of a GFP plasmid induced effective expression of the fluorescent protein in > 70% cells in the population. These outcomes were quantitatively assessed by confocal microscopy and flow cytometry. We also demonstrated that the enhanced cellular uptake of the non-toxic cationic MSNP enhance the delivery of the hydrophobic anticancer drug, paclitaxel, to pancreatic cancer cells. In summary, we demonstrate that by a careful selection of PEI size, it is possible to construct cationic MSNP that are capable of nucleotide and enhanced drug delivery with minimal or no cytotoxicity. This novel use of a cationic MSNP extends its therapeutic use potential.
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影响因子：
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