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Mesoporous core-shell silica nanoparticles with anti-fouling properties for ovarian cancer therapy
Chemical Engineering Journal ( IF 13.3 ) Pub Date : 2018-01-07 , DOI: 10.1016/j.cej.2017.12.116
Sandra Sanchez-Salcedo , Maria Vallet-Regí , Sophia Allaf Shahin , Carlotta A. Glackin , Jeffrey I. Zink

Mesoporous silica nanoparticles (MSNPs) have many potential applications in biomedical fields. However, when MSNPs are exposed to plasma, protein adsorption leads to opsonization and decreases blood circulation time. A new multifunctional nanodevice based on polyethylenimine (PEI) coated core-shell Fe3O4@SiO2 MSNPs with a zwitterionic 2-methacryloyloxyethyl phosphorylcholine (MPC) surface was designed to minimize unspecific protein adhesion. Particle size measurements demonstrated an excellent non-fouling capacity in solutions containing Bovine Serum Albumin (BSA) and Fetal Bovine Serum (FBS) plasma proteins. The system was used in this study to co-deliver two different cargos: siRNA and daunorubicin. Anti-TWIST siRNA plays critical role in modulating knockdown of TWIST and sensitizing cells to chemotherapeutics such as daunorubicin for ovarian cancer therapy. The drug was released in response to externally controlled oscillating magnetic fields (OMF). siRNA (siGFP) silenced expression of green fluorescence protein (GFP) in Ovcar8 cancer cells, demonstrating the incorporation of core shell MSNPs into cells and siGFP delivery. The synergistic effect of the co-release of anti-TWIST-siRNA loaded in the PEI and daunorubicin loaded in NPs’ pores caused increased cytotoxicity in Ovcar8 of up to 50% from both zwitteronic and non-zwitteronic NPs. The system is the first example of silencing by anti-TWITS-siRNA/daunorubicin co-delivered using zwitterionic core-shell nanoparticles with low-fouling adsorption. This engineered multifunctional approach may provide therapeutic potential for the treatment of currently incurable ovarian cancer.



中文翻译:

具有防污性能的中孔核-壳二氧化硅纳米粒子用于卵巢癌治疗

介孔二氧化硅纳米颗粒(MSNP)在生物医学领域具有许多潜在的应用。但是,当MSNP暴露于血浆时,蛋白质吸附会导致调理作用并缩短血液循环时间。基于聚乙烯亚胺(PEI)包覆的核-壳Fe 3 O 4 @SiO 2的新型多功能纳米器件设计具有两性离子2-甲基丙烯酰氧基乙基磷酰胆碱(MPC)表面的MSNP,以最大程度地减少非特异性蛋白的粘附。粒度测量表明,在含有牛血清白蛋白(BSA)和胎牛血清(FBS)血浆蛋白的溶液中具有出色的防污能力。该系统在本研究中用于共同交付两种不同的货物:siRNA和柔红霉素。抗TWIST siRNA在调节TWIST的敲低和使细胞对柔红霉素等化学疗法敏感的卵巢癌治疗中发挥关键作用。响应外部控制的振荡磁场(OMF)释放药物。siRNA(siGFP)沉默了Ovcar8癌细胞中绿色荧光蛋白(GFP)的表达,证明了核心壳MSNP掺入细胞和siGFP传递。PEI中装载的抗TWIST-siRNA和NPs孔中装载的柔红霉素的共同释放的协同效应导致两性和非两性NP的Ovcar8细胞毒性增加高达50%。该系统是通过使用低污垢吸附力的两性离子核壳纳米粒子共同递送的抗TWITS-siRNA /柔红霉素进行沉默的第一个实例。这种工程化的多功能方法可为治疗目前无法治愈的卵巢癌提供治疗潜力。该系统是通过使用低污垢吸附力的两性离子核壳纳米粒子共同递送的抗TWITS-siRNA /柔红霉素进行沉默的第一个实例。这种工程化的多功能方法可为治疗目前无法治愈的卵巢癌提供治疗潜力。该系统是通过使用低污垢吸附力的两性离子核壳纳米粒子共同递送的抗TWITS-siRNA /柔红霉素进行沉默的第一个实例。这种工程化的多功能方法可为治疗目前无法治愈的卵巢癌提供治疗潜力。

更新日期:2018-01-07
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