Abstract

Ultrasound-triggered phase transition sensitive nanodroplets with multimodal imaging functionality were prepared via premix Shirasu porous glass (SPG) membrane emulsification method. The nanodroplets with fluorescence dye DiR and SPIO nanoparticles (DiR-SPIO-NDs) had a polymer shell and a liquid perfluoropentane (PFP) core. The as-formed DiR-SPIO-NDs have a uniform size of 385±5.0 nm with PDI of 0.169±0.011. The TEM and microscopy imaging showed that the DiR-SPIO-NDs existed as core-shell spheres, and DiR and SPIO nanoparticles dispersed in the shell or core. The MTT and hemolysis studies demonstrated that the nanodroplets were biocompatible and safe. Moreover, the proposed nanodroplets exhibited significant ultrasound-triggered phase transition property under clinical diagnostic ultrasound irradiation due to the vaporization of PFP inside. Meanwhile, the high stability and R2 relaxivity of the DiR-SPIO-NDs suggested its applicability in MRI. The in vivo T2-weighted images of MRI and fluorescence images both showed that the image contrast in liver and spleen of rats and mice model were enhanced after the intravenous injection of DiR-SPIO-NDs. Furthermore, the ultrasound imaging (US) in mice tumor as well as MRI and fluorescence imaging in liver of rats and mice showed that the DiR-SPIO-NDs had long-lasting contrast ability in vivo. These in vitro and in vivo findings suggested that DiR-SPIO-NDs could potentially be a great MRI/US/fluorescence multimodal imaging contrast agent in the diagnosis of liver tissue diseases.

Highlights

  • Multimodal imaging has played an ever-increasing role in the diagnosis and prognosis of liver tissue diseases [1]

  • The results indicated that the size of NDs was enlarged, size distribution was broadened and the surface charge was changed from negative to positive when Superparamagnetic iron oxide (SPIO) and dioctadecyltetramethyl indotricarbocyanine iodide (DiR) were included

  • The vehicle acoustic nanodroplets DiR-SPIO-NDs with ultrasound-triggered phase transition were prepared by premix Shirasu porous glass (SPG) membrane emulsification method

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Summary

Introduction

Multimodal imaging has played an ever-increasing role in the diagnosis and prognosis of liver tissue diseases [1]. MRI is a soft-tissue contrast imaging modality with high spatial resolution and multi-planar imaging capacities, but its cost is relatively high and the imaging time is long with relatively low sensitivity. Fluorescence imaging is an imaging modality with high sensitivity and multicolor, but it is nonquantitative with poor tissue penetrating ability. To utilize the strengths of different imaging methods, multimodality imaging has become an attractive strategy for clinical research. The integration of several imaging contrast agents with different capabilities in multifunctional nanoparticles would obtain more accurate and reliable information about diseases through combining multimodal imaging [5]

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