Dendrosome Based Delivery of siRNA Against E6/E7 Oncogenes in Cervical Cancer

While siRNA treatment holds great promise for the treatment of cancers the field has been held back by the availability of suitable delivery vehicles. For cervical cancer the E6 and E7 oncogenes are ideal siRNA targets for treatment. The purpose of the present study was to explore the potential of dendrosomes for the delivery of siRNA targeting E6 and E7 proteins of cervical cancer cells, in vitro. Optimization of dendrimer generation (G) and Nitrogen/Phosphate (N/P) ratio was carried out using dendrimer:FITC oligo complexes. The optimized N/P ratios were used in formulating dendrimer-siGFP complexes. While formulation 4D100 displayed the highest GFP knockdown, it was also found to be highly toxic to cells. In the final formulation 4D100 was encapsulated into dendrosomes, in order to mask these toxic effects. The optimized dendrosomal formulation (DF), DF3 was found to possess a siGFP-entrapment efficiency of 49.76 ± 1.62 %, vesicle size of 154 ± 1.73 nm, and zeta potential of +3.21 ± 0.07 mV. The GFP knockdown efficiency of DF3 (dendrosome) was found to be almost identical to that of 4D100 (dendrimer:siRNA complex), but the former was completely non-toxic to the cells. DF3 containing siRNA against E6/E7 was found to knockdown the target genes considerably, as compared to the other formulations trialed. Our results suggest that dendrosomes hold potential for the delivery of siRNA and a suitable targeting strategy could be useful for applications in vivo.