Laser activatable perfluorocarbon bubbles for imaging and therapy through enhanced absorption from coupled silica coated gold nanoparticles

Abstract

Nanoparticles have extensively been used for cancer therapy and imaging (i.e., theranostics) using various imaging modalities. Due to their physical and chemical properties (e.g., absorption, fluorescence, and magnetic properties) they have been used for image guided therapy for cancer treatment monitoring. There are various limitations that make many theranostic agents unable to be used for the extended periods of time required for enhancing theranostic capabilities. Some of these are due to inherent characteristics (e.g., change and/or breakdown of structure) present upon continuous irradiation and others are due to environmental (i.e., physiological) conditions that can lead to physical instability (i.e., in terms of size) affecting the amount of particles that can accumulate at the target site and the overall contrast that can be achieved. In this study, perfluorohexane (PFH) nanoemulsions (NEs) were synthesized with silica coated gold nanoparticles (PFH-NEs-scAuNPs) in order to give both stable and enhanced signals for cancer imaging by increasing vaporization of the emulsions into bubbles through the process of optical droplet vaporization (ODV). The resulting perfluorohexane bubbles could be imaged using nonlinear ultrasound (NL US) which significantly increases the signal to noise ratio due to the nonlinear scattering properties of oscillating bubbles. The NL US signals from PFH bubbles were found to be more stable compared to conventional bubbles used for contrast imaging. In addition, the vaporization of PFH NEs into bubbles was shown to cause significant cancer cell death reflecting the theranostic capabilities of the formed PFH bubbles. Since cell death is initiated with laser excitation of PFH-NEs-scAuNPs, these nanoparticles can specifically target cancer cells once they have accumulated at the tumor region. Due to the type of theranostic agent and imaging modality used, the PFH-NEs-scAuNPs can be used to provide higher specificity compared to other agents for locating the tumor region by minimizing tissue specific signals while at the same time being used to treat cancer.