The packaging of siRNA within the mesoporous structure of silica nanoparticles
The packaging of siRNA within the mesoporous structure of silica nanoparticles
复制标题
二氧化硅纳米颗粒介孔结构内的 siRNA 包装
DOI：
10.1016/j.biomaterials.2011.08.068
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发表时间：
2011-12-01
期刊：
影响因子：
14
通讯作者：
Gu, Hongchen
中科院分区：
文献类型：
--
作者：
Li, Xu;Xie, Qian Reuben;Gu, Hongchen
介孔二氧化硅纳米颗粒 (MSN) 是一种很有前景的生物医学应用材料，例如将药物或生物分子（siRNA 或 DNA）输送到靶细胞或组织。 MSN 表面带有正电荷功能，已被用作 siRNA 递送的载体。然而，这种 siRNA 包装策略避免了利用介孔，因此阻碍了对递送载体表面的进一步修饰。为了解决这些问题，我们在强脱水溶液条件下成功地将siRNA包装到磁性介孔二氧化硅纳米粒子（M-MSNs）的介孔中。将装载 siRNA 的 M-MSN 与聚乙烯亚胺 (PEI) 混合，在其外表面上形成聚合物层。将获得的聚集体在酸性溶液中进一步超声处理，制备分散良好的siRNA递送载体(M-MSN_siRNA@PEI)。这种递送载体具有有效的siRNA保护作用和可忽略的细胞毒性，可以内化到癌细胞中并在细胞质中释放siRNA。在基因沉默实验中，这些递送载体高效介导外源增强型绿色荧光蛋白 (EGFP) 基因和内源 B 细胞淋巴瘤 2 (Bcl-2) 基因的敲低。总之，我们的 siRNA 包装策略扩展了 M-MSN 的应用潜力，并且所得的 siRNA 递送载体可以进一步测试用于体内实验。 (C) 2011 Elsevier Ltd. 保留所有权利。
Mesoporous silica nanoparticle (MSN) is a promising material for biomedical applications, such as delivering drugs or biological molecules (siRNA or DNA), to the target cells or tissues. With positive-charge functionalization on their surface, MSNs have already been used as vectors for siRNA delivery. Nevertheless, such siRNA packaging strategy avoids utilizing the mesopores and consequently hinders further modifications on the delivery vehicle surface. To solve these problems, we have successfully packaged siRNA into the mesopores of magnetic mesoporous silica nanoparticles (M-MSNs) under a strongly dehydrated solution condition. The siRNA-loaded M-MSNs were mixed with polyethyleneimine (PEI) to form a polymer layer on their external surface. The obtained aggregates were further treated by ultrasonication in acidic solution to prepare well dispersed siRNA delivery vehicles (M-MSN_siRNA@PEI). Such delivery vehicles, with effective siRNA protective effect and negligible cytotoxicity, could be internalized into cancer cells and release siRNA in the cytoplasm. In gene silencing experiments, these delivery vehicles mediated, with high efficiency, knockdown of both exogenous enhanced green fluorescent protein (EGFP) gene and endogenous B-cell lymphoma 2 (Bcl-2) gene. In summary, our siRNA packaging strategy extends the application potential of M-MSNs and the resulting siRNA delivery vehicles can be further tested for in vivo experiments. (C) 2011 Elsevier Ltd. All rights reserved.