Ultrasound-Responsive Nanoparticles for Continuous pH Sensing In Vivo

Abstract

Ultrasound (US) is one of the most commonly used medical imaging techniques. Contrast agents are administered to patients to improve fidelity of US images and for theranostic applications. The majority of current research into US contrast agents relies on microbubbles containing a phospholipid shell surrounding a gaseous core, as this leads to high degree of echogenicity. However, these materials only last for 5-30 minutes in vivo due to diffusion of the gas into the bloodstream. To our knowledge, the combination of ultrasound technology and contrast agents to create in vivo biosensors has not yet been investigated. In this work we designed and produced a pH-sensitive US contrast agent based on core-shell materials. Here we used a silica scaffold coated with Layer-by-Layer (LbL) polymer as the dynamic component (Figure 1). We found that following encapsulation of the hybrid particle in a silica shell, pH changes induced polymer rigidity changes which could be detected using standard clinical and pre-clinical ultrasound imaging systems. Herein we will describe the material design and characterisation, gel phantom ultrasound studies, and real-time in vivo biosensing of pH in the live animal. Such biosensors could find application in biomedical research and clinical diagnostics in deep tissue, providing real-time information without relying on laboratory infrastructure or complex imaging systems.