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Cellular delivery of plasmid DNA (pDNA) specifically into dendritic cells (DCs) has provoked wide attention in various applications. However, delivery tools that achieve effective pDNA transfection in DCs are rare. Herein, we report that tetrasulphide bridged mesoporous organosilica nanoparticles (MONs) have enhanced pDNA transfection performance in DC cell lines compared to conventional mesoporous silica nanoparticles (MSNs). The mechanism of enhanced pDNA delivery efficacy is attributed to the glutathione (GSH) depletion capability of MONs. Reduction of initially high GSH levels in DCs further increases the mammalian target of rapamycin complex 1 (mTORc1) pathway activation, enhancing translation and protein expression. The mechanism was further validated by showing that the increased transfection efficiency was apparent in high GSH cell lines but not in low GSH ones. Our findings may provide a new design principle of nano delivery systems where the pDNA delivery to DCs is important.

Mesoporous Organosilica Nanoparticles with Tetrasulphide Bond to Enhance Plasmid DNA Delivery