Dual-mode US/MRI nanoparticles delivering siRNA and Pt(iv) for ovarian cancer treatment.
Dual-mode US/MRI nanoparticles delivering siRNA and Pt(iv) for ovarian cancer treatment.
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双模式 US/MRI 纳米颗粒递送 siRNA 和 Pt(iv) 用于卵巢癌治疗
作者：
众所周知，卵巢癌是致死率最高的妇科恶性肿瘤。以铂类为主的抗肿瘤药物是卵巢癌的一线化疗药物。然而，由于铂的剂量限制性毒性，它们的治疗效率受到严重限制。非常需要新的治疗诊断策略来克服化疗毒性。同时，实时治疗效果对于医生来说是不可见的。在此，我们构建了 PFH/siRNA/Fe3O4@Pt(iv) NPs-cRGD (NPs-cRGD)，用于通过实时成像对卵巢肿瘤进行精确治疗诊断。 NPs-cRGD具有良好的储存稳定性并能抵抗血清诱导的聚集，有利于药物递送。此外，凝胶延迟测定表明，NPs-cRGD 对 siRNA 表现出强大的保护作用，以抵抗核酸酶降解。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，纳米粒子-cRGD与US表现出优异的抗肿瘤治疗效率，这是由于cRGD配体和US暴露增强了细胞摄取效率。因此，这项工作中的双模式纳米粒子可以为各种多模式纳米平台的开发提供宝贵的见解，这些多模式纳米平台可传递药物或基因，以针对各种癌症进行精确的治疗诊断。
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/Fe3O4@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.
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