title: The packaging of siRNA within the mesoporous structure of silica nanoparticles.
abstract: 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.
authors: Nano Biomedical Research Center, School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China.
authors: Xu
authors: X
authors: Li
authors: Qian Reuben
authors: QR
authors: Xie
authors: Jixi
authors: J
authors: Zhang
authors: Weiliang
authors: W
authors: Xia
authors: Hongchen
authors: H
authors: Gu
mesh_terms: D000327:Adsorption; D016923:Cell Death; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000378:metabolism; D019610:Cytoprotection; D004339:Drug Compounding; D004587:Electrophoresis, Agar Gel; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D060328:Magnetic Phenomena; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D011094:Polyethyleneimine / Q000737:chemistry; D016062:Porosity; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism*; D012822:Silicon Dioxide / Q000737:chemistry*
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D012822:Silicon Dioxide; D011094:Polyethyleneimine