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Dual-mode US/MRI nanoparticles delivering siRNA and Pt(iv) for ovarian cancer treatment

机译:提供siRNA和Pt(iv)的双模式US / MRI纳米颗粒用于卵巢癌治疗

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As known to all, ovarian cancer ranks the most lethal of the gynecological malignancies. The antitumor drugs based on platinum are first-line chemotherapy drugs for ovarian cancer. However, their therapeutic efficiency is severely limited owing to dose-limiting toxicities of platinum. New theranostic strategies to overcome chemotherapy toxicity is highly desirable. Meanwhile, the real-time treating effect is not visible for doctors. Herein, we constructed PFH/siRNA/Fe _(3) O _(4) @Pt( IV ) NPs-cRGD (NPs-cRGD) for precise theranostics against ovarian tumors with real-time imaging. The NPs-cRGD had a good storage stability and resisted the serum-induced aggregation, which was beneficial for drug delivery. Additionally, gel-retardation assay demonstrated that the NPs-cRGD exhibited great protection to siRNA to resist nuclease degradation. In vitro , the NPs-cRGD showed good dual-mode US/MRI imaging and the relative imaging research was also discussed. Moreover, the in vitro experiments indicated that the NPs-cRGD with US exhibited excellent antitumor therapeutic efficiency, resulting from the cRGD ligands and US exposure enhanced the cellular uptake efficiency. Thus, the dual-mode nanoparticles in this work may provide precious insight into the development of various multi-mode nanoplatforms delivering drugs or genes for precise theranostics against various cancer.
机译:众所周知,卵巢癌是最致命的妇科恶性肿瘤。基于铂的抗肿瘤药物是用于卵巢癌的一线化疗药物。然而,由于铂的剂量限制毒性,其治疗效率受到严重限制。克服化学疗法毒性的新治疗方法非常需要。同时,医生看不到实时治疗效果。在这里,我们构建了PFH / siRNA / Fe _(3)O _(4)@Pt(IV)NPs-cRGD(NPs-cRGD),用于通过实时成像精确地治疗卵巢肿瘤。 NPs-cRGD具有良好的储存稳定性,并能抵抗血清诱导的聚集,有利于药物的递送。此外,凝胶延迟试验表明,NPs-cRGD对siRNA表现出强大的保护作用,可抵抗核酸酶降解。在体外,NPs-cRGD表现出良好的双模式US / MRI成像,并讨论了相关成像研究。此外,体外实验表明,具有US的NPs-cRGD表现出优异的抗肿瘤治疗效率,这是由于cRGD配体和US暴露提高了细胞摄取效率。因此,这项工作中的双模纳米颗粒可以为开发多种多模纳米平台的研究提供宝贵的见识,这些平台可以提供药物或基因来精确治疗各种癌症。

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