Abstract
For cancer diagnosis, a paramount challenge still exists in the exploring of methods that can precisely discriminate tumor tissues from their surrounding healthy tissues with a high target-to-background signal ratio. Here, we report a NaGdF4@CaCO3-PEG core-shell nanoparticle which has the tumor acidic microenvironment enhanced imaging signals of ultrasound and magnetic resonance. Under the acidic conditions, the CaCO3 shell will gradually dissolve which then facilitate the interaction of NaGdF4 with the external aqueous environment to enhance water proton relaxation. Meanwhile, the CO2 bubbles generated by the CaCO3 dissolvement will generate strong elastic echo for US detection. The core-shell structure of NaGdF4@CaCO3-PEG can be observed by TEM, and its composition can be determined by STEM. The acid triggered generation of CO2 bubbles and the enhancement of MRI signal could be demonstrated in vitro, and the excellent dual-modal magnetic resonance/ultrasonic cancer imaging abilities of NaGdF4@CaCO3-PEG could be also proved at the tumor site in vivo. The here described proof-of-concept nanoparticles with pH triggered magnetic resonance/ultrasonic dual-modal imaging enhancement, may serve as a useful guide to develop various molecular imaging strategies for cancer diagnosis in the future.
Highlights
Cancer is becoming to one of the most dreaded disease and still remains as a major threat to human life[1]
The hydrophobic NaGdF4@CaCO3-PEG to that of core-only (NaGdF4) will transfer from oil phase to water droplets as the surfactants can self-assemble on these nanoparticles
The hydrophilic groups of the surfactants has a well affinity with Ca2+ which could recruit these ions on the surfaces of the NaGdF4 nanoparticles
Summary
Cancer is becoming to one of the most dreaded disease and still remains as a major threat to human life[1]. Developing a sensitive dual modal imaging (US and MRI) agent would make them as favorable tools for precisely visualizing biological and physiological changes with high signal-to-noise ratio, and would render synergistic efficacy to overcome their own inherent limitations[31]. As for a new type of US contrast agent, CaCO3 nanoparticles with rigid structure can penetrate into host tumoral environments for cancer imaging, while the frequently used gas-filled microbubbles suffer from inherent drawbacks, such as low stability, short half-life in blood and low penetration ability due to the large size, which is limited to the imaging of intravascular structures. The shell of CaCO3 was deposited onto the core surface of NaGdF4 nanoparticles through the microemulsion method; in addition, physicochemical properties of nanoscale systems, such as size, dispersibility, and toxicity were systematically analyzed; the US and MRI imaging enhanced efficiency were both evaluated in vitro and in vivo, which clearly proved that our probe could be utilized for sensitive and specific tumor imaging with responding to extracellular acidic microenvironments
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