13048-33-4Relevant articles and documents
Bioreducible poly (β-amino esters)/shRNA complex nanoparticles for efficient RNA delivery
Yin, Qi,Gao, Yu,Zhang, Zhiwen,Zhang, Pengcheng,Li, Yaping
, p. 35 - 44 (2011)
RNA interference (RNAi) mediating gene silencing is a promising approach in the area of gene therapy, but it still is a major challenge to find new non-viral vectors with high transfection efficiency and low toxicity until today. In this work, three novel bioreducible poly (β-amine esters) (PAEs) with different amino monomers in the main chain were designed and synthesized by Michael addition polymerization. All PAEs could condense shRNA into complex nanoparticles with particle size (60-200 nm) and positive surface charges (>+10 mV). The PAEs/shRNA complex nanoparticles (PAENs) were stable under the extracellular physiological condition, while it would degrade in the reductive environment due to the cleavage of the disulfide bonds in the PAEs main chain. PAENs could achieve efficient cellular uptake and EGFP silencing in HEK-293 cells and U-87 MG cells with low cytotoxicity. The high accumulation of PAENs in tumor and high silencing efficiency of intra-tumor EGFP expression occurred when PAENs were intravenously injected into BALB/c mice bearing U-87 MG-GFP tumor. The relationship between the polymer structure and RNAi efficiency and cytotoxicity showed that the density of nitrogen atoms in PAEs backbone and the existence of disulfide bonds demonstrated the remarkable influence on in vitro and in vivo gene silencing efficiency and cytotoxicity. These experimental results suggested that the PAENs could be a promising non-viral vector for efficient RNA delivery.
In situ fabrication of paclitaxel-loaded core-crosslinked micelles via thiol-ene "click" chemistry for reduction-responsive drug release
Huang, Ying,Sun, Rui,Luo, Qiaojie,Wang, Ying,Zhang, Kai,Deng, Xuliang,Zhu, Weipu,Li, Xiaodong,Shen, Zhiquan
, p. 99 - 107 (2016)
In this study, a facile method to fabricate reduction-responsive core-crosslinked micelles via in situ thiol-ene "click" reaction was reported. A series of biodegradable poly(ether-ester)s with multiple pendent mercapto groups were first synthesized by melt polycondensation of diol poly(ethylene glycol), 1,4-butanediol, and mercaptosuccinic acid using scandium trifluoromethanesulfonate [Sc(OTf)3] as the catalyst. Then paclitaxel (PTX)-loaded core-crosslinked (CCL) micelles were successfully prepared by in situ crosslinking hydrophobic polyester blocks in aqueous media via thiol-ene "click" chemistry using 2,2′-dithiodiethanol diacrylate as the crosslinker. These PTX-loaded CCL micelles with disulfide bonds exhibited reduction-responsive behaviors in the presence of dithiothreitol (DTT). The drug release profile of the PTX-loaded CCL micelles revealed that only a small amount of loaded PTX was released slowly in phosphate buffer solution (PBS) without DTT, while quick release was observed in the presence of 10.0 mM DTT. Cell count kit (CCK-8) assays revealed that the reduction-sensitive PTX-loaded CCL micelles showed high antitumor activity toward HeLa cells, which was significantly higher than that of reduction-insensitive counterparts and free PTX. This kind of biodegradable and biocompatible CCL micelles could serve as a bioreducible nanocarrier for the controlled antitumor drug release.
Hydroxy functional acrylate and methacrylate monomers prepared via lipase-catalyzed transacylation reactions
Popescu, Dragos,Hoogenboom, Richard,Keul, Helmut,Moeller, Martin
experimental part, p. 80 - 89 (2010/08/20)
Candida antarctica lipase B (CAL-B, Novozyme 435) catalyzes the transacylation of methyl acrylate and methyl methacrylate with diols and triols in 2-methyl-2-butanol at 50 °C. Under the experimental conditions, up to 70 mol% of the acyl donor methyl acrylate was converted. Methyl methacrylate is the less efficient acyl donor (up to 60 mol%) due to the higher sterical hindrance in the enzymatic transacylation. Under the reaction conditions high yields of the mono-acylated products are obtained, which contain minor amounts of bis(meth)acrylates. In addition it was observed that Novozyme 435 catalyzes regioselectively the acylation of the primary hydroxyl groups. In comparison with the chemical catalyzed route no selectivity was observed for unsubstituted diols. For substituted diols more mono-acylated product was formed in the lipase-catalyzed reaction than in the chemical catalyzed reaction.
