Nano Biomedical Research Center, School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China.
Biomaterials. 2011 Dec;32(35):9546-56. doi: 10.1016/j.biomaterials.2011.08.068. Epub 2011 Sep 8.
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.
介孔硅纳米颗粒（MSN）是一种很有前途的生物医学应用材料，可将药物或生物分子（siRNA 或 DNA）递送到靶细胞或组织。通过在其表面进行正电荷功能化，MSNs 已经被用作 siRNA 传递的载体。然而，这种 siRNA 包装策略避免了利用介孔，从而阻碍了递药载体表面的进一步修饰。为了解决这些问题，我们已经成功地在强烈脱水溶液条件下将 siRNA 包装到磁性介孔硅纳米颗粒（M-MSNs）的介孔中。负载 siRNA 的 M-MSNs 与聚乙烯亚胺（PEI）混合，在其外表面形成聚合物层。所得的聚集体在酸性溶液中进一步通过超声处理，制备出分散良好的 siRNA 递药载体（M-MSN_siRNA@PEI）。这种递药载体具有有效的 siRNA 保护作用和可忽略的细胞毒性，可被癌细胞内化并在细胞质中释放 siRNA。在基因沉默实验中，这些递药载体以高效率介导了外源性增强型绿色荧光蛋白（EGFP）基因和内源性 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-MSNs 的应用潜力，所得的 siRNA 递药载体可以进一步进行体内实验的测试。
