Curcumin-Loaded Nanoparticles with Low-Intensity Focused Ultrasound-Induced Phase Transformation as Tumor-Targeted and pH-Sensitive Theranostic Nanoplatform of Ovarian Cancer.

We have developed a simple and versatile nanoplatform using pH-sensitive ferritin nanocages co-loaded with the anticancer drug curcumin (Cur) and liquid fluorocarbon perfluorohexane (PFH) inside the core and conjugated tumor-targeting molecule FA outside the shell referred to as FA-FCP. The synthesized FA-FCP has an average particle diameter of 47 nm, with stable and favorable physicochemical properties in different media, and high biocompatibility and biosafety in vivo and in vitro. Under the conditions of low-intensity focused ultrasound (LIFU) and at pH = 5.0, FA-FCP released a large amount of drugs (53.2%) in 24 h. After 4 min of LIFU (7 W) treatment, FA-FCP provided contrast-enhanced ultrasound imaging capabilities at pH = 5.0. Due to FA receptor-mediated endocytosis, FA-FCP could efficiently enter the cells and further relocate to lysosomes. Eighteen hours after injection of FA-FCP, the tumor was stimulated by LIFU, resulting in a contrast-enhanced ultrasound image. In vivo and in vitro experiments showed that the combined use of FA-FCP and LIFU had significant tumor treatment effects. Based on the results, it was concluded that FA-FCP combined with the external LIFU and the endogenic acidic environment can have powerful theranostic functions and provide a novel type of non-invasive and integrated tumor theranostic option.