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

Abstract

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.