Pharmaceutical NanotechnologyAmmonium salt modified mesoporous silica nanoparticles for dual intracellular-responsive gene delivery

Effective gene delivery system plays an importmant role in the gene therapy. Mesoporous silica nanoparticle (MSN) has become one potential gene delivery vector because of its high stability, good biodegradability and low cytotoxicity. Herein, MSN-based dual intracellular responsive gene delivery system CMSN-A was designed and fabricated. Short chain ammonium group, which is modified with disulfide bond and amide bond simultaneously, is facilely grafted onto the mesoporous silica nanoparticles. As-synthesized CMSN-A is endowed with small size (80-110 nm), large conical pores (15-23 nm), and moderate Zeta potential (+25 ± 2 mV), which behaves high gene loading capacity, good stability and effectively gene transfection. Moreover, CMSN-A exhibits dual micro-environment responsive (lower pH, more reducing substances) due to the redox-sensitive disulfide bond and pH-sensitive amide bond in the short chain ammonium group. The cellular uptake study indicates that CMSN-A could transfer both plasmid DNA (pDNA) and siRNA into different kinds of tumour cells, which demonstrate the promising potential of CMSN-A as effective and safe gene-delivery vectors.

Short chain ammonium group, which is modified with disulfide bond and amide bond simultaneously, is modified into the small-sized mesoporous nanoparticles with large conical pore (CMSN-A) for dual-responsive gene delivery.128