Enhancing Structural Stability of Oil-Shell Microbubbles via Incorporation of a Gold Nanoparticle Protective Shell for Theranostic Applications

Phospholipid-stabilized microbubbles are utilized as contrast agents in medical ultrasound imaging, and researchers are currently investigating their potential as theranostic agents. Due to the inadequate water solubility and poor stability of numerous new therapeutics, the development of stable microbubbles with the capacity to encapsulate hydrophobic therapeutics is necessary. Herein, we proposed a flow-focusing microfluidic device to generate highly monodispersed, phospholipid-stabilized dual-layer microbubbles for theranostic applications. The stability and microstructural evolution of these microbubbles were investigated by microscopy and machine-learning-assisted segmentation techniques at different phospholipid and gold nanoparticle concentrations. The double-emulsion microbubbles, formed with the combination of phospholipids and gold nanoparticles, developed a protective gold nanoparticle shell that not only acted as a steric barrier against gas diffusion and microbubble coalescence but also alleviated the progressive dewetting instability and the subsequent cascade of coalescence events.