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    Dynamic Solid-State Ultrasound Contrast Agent for Monitoring pH Fluctuations In Vivo

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    Author
    Walker, JA-T; Wang, X; Peter, K; Kempe, K; Corrie, SR
    Date
    2020-04-24
    Source Title
    ACS sensors
    Publisher
    AMER CHEMICAL SOC
    University of Melbourne Author/s
    Wang, Xiaowei
    Affiliation
    Melbourne Medical School
    Metadata
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    Document Type
    Journal Article
    Citations
    Walker, J. A. -T., Wang, X., Peter, K., Kempe, K. & Corrie, S. R. (2020). Dynamic Solid-State Ultrasound Contrast Agent for Monitoring pH Fluctuations In Vivo. ACS SENSORS, 5 (4), pp.1190-1197. https://doi.org/10.1021/acssensors.0c00245.
    Access Status
    Access this item via the Open Access location
    URI
    http://hdl.handle.net/11343/254201
    DOI
    10.1021/acssensors.0c00245
    Open Access URL
    http://doi.org/10.1021/acssensors.0c00245
    Abstract
    The key challenge for in vivo biosensing is to design biomarker-responsive contrast agents that can be readily detected and monitored by broadly available biomedical imaging modalities. While a range of biosensors have been designed for optical, photoacoustic, and magnetic resonance imaging (MRI) modalities, technical challenges have hindered the development of ultrasound biosensors, even though ultrasound is widely available, portable, safe, and capable of both surface and deep tissue imaging. Typically, contrast-enhanced ultrasound imaging is generated by gas-filled microbubbles. However, they suffer from short imaging times because of the diffusion of the gas into the surrounding media. This demands an alternate approach to generate nanosensors that reveal pH-specific changes in ultrasound contrast in biological environments. Silica cores were coated with pH-responsive poly(methacrylic acid) (PMASH) in a layer-by-layer (LbL) approach and subsequently covered in a porous organosilica shell. Transmission electron microscopy (TEM) and confocal laser scanning microscopy (CLSM) were employed to monitor the successful fabrication of multilayered particles and prove the pH-dependent shrinkage/swelling of the PMASH layer. This demonstrates that reduction in pH below healthy physiological levels resulted in significant increases in ultrasound contrast, in gel phantoms, mouse cadaver tissue, and live mice. The future of such materials could be developed into a platform of biomarker-responsive ultrasound contrast agents for clinical applications.

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