title: Triblock copolymer-encapsulated nanoparticles with outstanding colloidal stability for siRNA delivery.
abstract: A new generation of siRNA nanocarrier with compact, uniform size and excellent colloidal stability has been developed by combining inorganic nanoparticles with rationally designed triblock copolymers. In contrast to conventional cationic polymers and nanoparticles that often condense oligonucleotides into polydisperse aggregates, our nanoparticle-polymer complexes remain single after loading with siRNA. More importantly, they are highly stable even in complete serum, which fills the gap between in vitro technology development using serum-free (or low percentage serum) cell culture media and downstream in vivo applications. Targeted delivery is achieved in GFP-expressing HeLa cells by functionalizing the siRNA delivery vehicle with an integrin-specific peptide ligand. The GFP positive cell population can be reduced from the original 86 to 60 and 25% for nontargeted and targeted nanoparticle-polymer complexes, respectively. At the nanocarrier concentration for siRNA delivery, virtually no cytotoxicity was detected. Further development and validation of this technology by introducing biodegradable and biocompatible core particles and testing them in lab animals could enable widespread uses of siRNA and potentially lead to clinical translation.
authors: Department of Bioengineering, University of Washington, Seattle, Washington 98195, USA.
authors: Jian
authors: J
authors: Qian
authors: Xiaohu
authors: X
authors: Gao
mesh_terms: D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000295:instrumentation / Q000379:methods*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism
chemical_list: D004337:Drug Carriers; D011108:Polymers; D034741:RNA, Small Interfering; D049452:Green Fluorescent Proteins