Polyethylenimine Functionalized Ultrasmall Mesoporous Silica Nanoparticles for siRNA Delivery
Graphical An ultrasmall mesoporous silica delivery system (∼8 nm) with PEG and PEI dual-modification (FMSNs-PEG@PEI) was developed for loading negatively charged siRNA through electrostatic interaction. FMSNs-PEG@PEI can efficiently deliver siRNA into 293T cells and protect siRNA from being degraded. In addition, when GAPDH related gene was delivered by FMSNS-PEG@PEI, we observed a lower expression in GAPDH gene knockdown cells. This study offers new possibilities for advanced gene delivery research and gene therapy by using ultra-small mesoporous silica nanoparticles with minor cellular toxicity. Small interfering RNA (siRNA) for gene therapy has attracted great attention. However, due to easy degradation and inaccessibility to the cells, the gene silencing efficiency is not always satisfactory. To overcome this hurdle, developing an excellent nanocarrier to deliver siRNA into cancer cells is crucial. Fluorescent mesoporous silica nanoparticles are considered to be a superb nanocarrier for siRNA delivery systems because of its negligible toxicity and good biocompatibility. Herein, we developed an efficient fluorescent ultrasmall mesoporous silica nanocarrier for siRNA loading and delivery. The ultrasmall nanocarriers with polyethylenimine coating have a uniform size of about 10 nm. We find that the amino groups on polyethylenimine can protect siRNA from being degraded. Based on the fluorescence observation, we show that polyethylenimine-coated mesoporous silica nanocarrier loaded with siRNA can be uptake by 293T cells. Importantly, we also prove that siRNA can be delivered into 293T cells by our nanocarrier and subsequently inhibit the expression of related genes. The study provides insights into the development of nonviral fluorescence nanocarriers for siRNA delivery, which have important implications for targeted cancer therapy.
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