期刊
COLLOIDS AND SURFACES B-BIOINTERFACES
卷 127, 期 -, 页码 155-163出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.colsurfb.2015.01.034
关键词
siRNA-PLGA conjugates; STAT3; Chitosan oligosaccharide (CSO); Micelles; Gene knockdown
资金
- National Natural Science Foundation of China, General Program [81173000, 81101661, 81200428]
- Natural Science Foundation of Zhejiang Province, China [LY14H300005]
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 200nm. 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. (C) 2015 Elsevier B.V. All rights reserved.
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