Enhanced delivery of gold nanoparticles by acoustic cavitation for photoacoustic imaging and photothermal therapy

Gold-nanorods incorporated with microbubbles (AuMBs) were introduced as a photoacoustic/ultrasound dual- modality contrast agent in our previous study. The application can be extended to theragnosis purpose. With the unique physical characteristics of AuMBs, we propose an enhanced delivery method for the encapsulated particles. For example, laser thermotherapy mediated by plasmonic nanoparticles can be made more effective by using microbubbles as a targeted carrier and acoustic cavitation for enhanced sonoporation. The hypothesis was experimentally tested. Firts, these AuMBs first act as molecular probes with binding to specific ligands. The improved targeting efficacy was macroscopically observed by an ultrasound system. The extended retention of targeted AuMB was observed and recorded for 30 minutes in a CT-26 tumor bearing mouse. Secondly, cavitation induced by time-varying acoustic field was also applied to disrupt the microbubbles and cause increased transient cellular permeability (a.k.a., sonoporation). Multimodal optical microscope based on a Cr:forsterite laser was used to directly observe these effects. The microscope can acquired third-harmonic generation (THG) and two-photon fluorescent (2PF) signals produced by the AuMBs. In vitro examination shows approximately a 60% improvement in terms of fluorescence signals from the cellular uptake of gold nanoparticles after sonoporation treatment. Therefore, we conclude that the controlled release is feasible and can further improve the therapeutic effects of the nanoparticles.