The packaging of siRNA within the mesoporous structure of silica nanoparticles

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.