期刊
BIOMATERIALS
卷 145, 期 -, 页码 154-167出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2017.08.036
关键词
PLGA nanoparticles; Polyethylenimine; Double emulsion solvent diffusion; Osteopontin; siRNA; Mammary carcinoma
资金
- Israel Science Foundation (ISF-NSFC program) [2648/16]
siRNA-loaded nanoparticles (NPs) administered systemically can overcome the poor stability and rapid elimination of free double-stranded RNA in circulation, resulting in increased tumor accumulation and efficacy. siRNA against osteopontin (siOPN), a protein involved in breast cancer development, was encapsulated in poly(D,L-lactic-co-glycolic acid) NPs by a double emulsion solvent diffusion (DESD) technique. We also compared the effect of polyethylenimine (PEI) molecular weight (800 Da and 25 kDa), used as the counter-ion for siRNA complexation, on the physicochemical properties of the NPs, cytotoxicity, and cellular uptake. NPs prepared by the DESD technique were obtained at the desired size(similar to 170 nm) using both types of PEIs, and were characterized with a neutral surface charge, high encapsulation yield (up to similar to 60%), siOPN concentration of 5.6-8.4 mu g/mg, stability in physiologic conditions in vitro and in vivo, and long-term shelf-life stability (> 3 years). The NPs prepared using both PEls exhibited no cytotoxicity in primary smooth muscle culture, and no detrimental effect on mice liver enzymes following their IV administration. Following cellular uptake and biodistribution studies, the therapeutic potential of the NPs was demonstrated by a significant decrease of tumor progression and size in an ectopic xenograft model of mammary carcinoma in mice. (C) 2017 Elsevier Ltd. All rights reserved.
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