Knockdown of STAT3 expression in SKOV3 cells by biodegradable siRNA–PLGA/CSO conjugate micelles

Biodegradable and biocompatible poly( d,l -lactic- co -glycolic acid) (PLGA)was conjugated to the 5′-thiol end of signal transducer and activator of transcription 3 (STAT3) small interfering RNA (STAT3–siRNA) via a disulfide bond. In aqueous environments, these siRNA–PLGA conjugates can spontaneously form core/shell type spherical micelles with a particle size of about 200   nm. A biodegradable, low molecular weight cationic polymer, chitosan oligosaccharide (CSO), was added to the siRNA–PLGA micelles at different nitrogen to phosphate (N/P) ratios to form stable, spherical siRNA–PLGA/CSO micelles with sizes of 150–180   nm. The siRNA–PLGA/CSO micelles were produced via ionic complexation between negatively charged siRNA and positively charged CSO on the outer shell of the micelles. The siRNA–PLGA/CSO micelles exhibited superior cellular uptake and STAT3 gene silencing efficiency in SKOV3 ovarian cancer cells when compared with siRNA/CSO complexes at the same N/P ratios with no significant differences with lipofectamine 2000. Furthermore, the siRNA–PLGA/CSO micelles showed that the efficiencies of cellular uptake and STAT3 gene silencing gradually increased with increasing N/P ratios. The siRNA–PLGA/CSO micelles also inhibited the growth of SKOV3 cells, as well as, promoted apoptosis of the cells. These results indicate that siRNA–PLGA/CSO micelles can be utilized as a novel and efficient siRNA carrier to treat a variety of diseases.