Enhanced small interfering RNA delivery into cells by exploiting the additive effect between photo-sensitive peptides...

To enhance the targeting delivery efficiency of small interfering RNA (siRNA) to tumour cells, a novel multifunctional liposome (PSP/NGR-L) comodified with photo-sensitive cell-penetrating peptides (PSP) and asparagine-glycine-arginine peptide (NGR) was constructed and investigated.

PSP was conjugated to 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-maleimide(polyethylene glycol)-2000 (DSPE-PEG2000 -MAL) to generate DSPE-PEG2000 -PSP and used to form PSP/NGR-L, the features of the liposomes were determined. HT-1080 and MCF-7 cells were used for cellular uptake tests, and the cellular uptake pathways were identified. Intracellular trafficking and endosomal escape were also evaluated. In-vitro siRNA transfection evaluations were carried out in HT-1080 cells.

The encapsulation efficiencies of liposomes were about 80%, and the mean particle sizes were around 100 nm. The targeting specificity of PSP/NGR-L was significantly enhanced via NGR navigation and ultraviolet (UV) light illumination. The internalization of PSP/NGR-L in HT-1080 cells was mediated by more than one cellular uptake mechanisms. The constructed nanocarrier could escape from the endosome to produce its effects in the cellular cytoplasm with the help of UV illumination. PSP/NGR-L could down-regulate expression of c-myc and augmented cell apoptosis in HT-1080 cells.

The application of combined PSP and NGR modifications may be a new approach for the selectively targeted delivery of siRNA to cancer cells.