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Figure 1.

Schematic diagram of the designed ultrasound-triggered phase transition DiR-SPIO-NDs with multimodal imaging functionality.

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Figure 2.

Stepwise fabrication of DiR-SPIO nanodroplets suspension.

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Figure 3.

The size distribution and morphology of nanodroplets.

Size distributions of (a) NDs and (b) DiR-SPIO-NDs. (c) Stability of NDs in normal saline. (d) TEM image of nanodroplets without fluorescence dye DiR and SPIO nanoparticles (bar = 1000 nm), (f) TEM image of DiR-SPIO-NDs (bar = 200 nm), and (e) and (g) are the magnified views (bar = 100 nm) of a portion (red frame) of (d) and (f), respectively.

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Figure 4.

Magnetic properties of DiR-SPIO-NDs and hydrophilic SPIO nanoparticles.

(a) T2-weighted MR images; (b) T2 relaxation rate (1/T2, s−1).

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Figure 5.

Ultrasound-triggered phase transition of DiR-SPIO-NDs in vitro.

(a–d) The ultrasound imaging of the different samples in vitro by using 3.5 MHz ultrasound transducer in TAD mode: (a) Before injection of samples, and after injection of (b) normal saline, (c) SonoVue, (d) DiR-SPIO-NDs; the left was B-mode image and the right was the corresponding contrast image in each picture. (e–f) Microscopy images (400×) of diluent DiR-SPIO-NBs after sonication for 2 min at 37°C. (e) Bright field, (f) fluorescence field.

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Figure 6.

Biocompatibility of DiR-SPIO-NDs.

MTT assay results for (a) HepG2 cells and (b) HL-7702 cells after incubation 24 h and 48 h. (c) Hemolysis assay results. Data were expressed as mean ± SD (n = 5).

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Figure 7.

In vivo fluorescence imaging in nude mice before and after intravenous injection of DiR-SPIO-NDs.

(a) Time-dependent images of DiR-SPIO-NDs in mice ventral views, (b) ex vivo images of organs harvested from the mice at 30 h after injection.

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Figure 8.

In vivo MRI in SD rat before and after intravenous injection of DiR-SPIO-NDs.

(a) T2-weighted images of rats at different time points before and after tail vein administration of DiR-SPIO-NDs; (b) Relative signal enhancement values in liver, spleen, kidney, and muscle before and after the injection of DiR-SPIO-NDs. (c–f) Prussian blue stained images (400×) of (c) liver, (d) spleen, (e) kidney and (f) lung after 8 h with the tail vein injection of DiR-SPIO-NDs.

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Figure 9.

In vivo B-mode ultrasound images of subcutaneous tumor with injection of DiR-SPIO-NDs.

Ultrasound images were obtained with Logiq9 system with a 9L linear transducer at 8.0(a) Before the injection, (b) 1 min after injection, (c) 4.5 h after injection. The red circle denoted the echo enhancement in the tumor region.

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