title: Knockdown of STAT3 expression in SKOV3 cells by biodegradable siRNA-PLGA/CSO conjugate micelles.
abstract: 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.
authors: College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China.
authors: Yunchun
authors: Y
authors: Zhao
authors: Women's Hospital, Medicine of School, Zhejiang University, Hangzhou 310006, China. Electronic address: chzheng@zju.edu.cn.
authors: Caihong
authors: C
authors: Zheng
authors: The Second Hospital, Medicine of School, Zhejiang University, Hangzhou 310058, China.
authors: Li
authors: L
authors: Zhang
authors: Women's Hospital, Medicine of School, Zhejiang University, Hangzhou 310006, China.
authors: Yue
authors: Y
authors: Chen
authors: Women's Hospital, Medicine of School, Zhejiang University, Hangzhou 310006, China.
authors: Yiqing
authors: Y
authors: Ye
authors: Women's Hospital, Medicine of School, Zhejiang University, Hangzhou 310006, China.
authors: Mengdan
authors: M
authors: Zhao
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001672:Biocompatible Materials / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D055785:Gene Knockdown Techniques; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D008823:Micelles; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D066244:Proton Magnetic Resonance Spectroscopy; D034741:RNA, Small Interfering / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D055672:Static Electricity; D014162:Transfection
chemical_list: D001672:Biocompatible Materials; D008823:Micelles; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D048271:Chitosan
keywords: Chitosan oligosaccharide (CSO); Gene knockdown; Micelles; STAT3; siRNA–PLGA conjugates