Mesoporous Organosilica Nanoparticles with Tetrasulphide Bond to Enhance Plasmid DNA Delivery
Yue Zhang,
He Xian,
Ekaterina Strounina,
Kimberley S. Gunther,
Matthew J. Sweet,
Chen Chen,
Chengzhong Yu,
Yue Wang
Affiliations
Yue Zhang
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia
He Xian
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia
Ekaterina Strounina
Centre for Advanced Imaging, The University of Queensland, Brisbane, QLD 4072, Australia
Kimberley S. Gunther
Institute for Molecular Bioscience (IMB), IMB Centre for Inflammation and Disease Research, and Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, QLD 4072, Australia
Matthew J. Sweet
Institute for Molecular Bioscience (IMB), IMB Centre for Inflammation and Disease Research, and Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, QLD 4072, Australia
Chen Chen
School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4072, Australia
Chengzhong Yu
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia
Yue Wang
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia
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.
