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.
This study investigates a photoacoustic/ultrasound dual-modality contrast agent, including extending its applications from image-contrast enhancement to combined diagnosis and therapy with site-specific targeting. The contrast agent comprises albumin-shelled microbubbles with encapsulated gold nanorods (AuMBs). The gas-filled microbubbles, whose diameters range from submicrometer to several micrometers, are not only echogenic but also can serve as drug-delivery vehicles. The gold nanorods are used to enhance the generation of both photoacoustic and photothermal signals. The optical absorption peak of the gold nanorods is tuned to 760 nm and is invariant after microbubble encapsulation. Dual-modality contrast enhancement is first described here, and the applications to cellular targeting and laser-induced thermotherapy in a phantom are demonstrated. Photoacoustic imaging can be used to monitor temperature increases during the treatment. The targeting capability of AuMBs was verified, and the temperature increased by 26°C for a laser power of 980 mW, demonstrating the potential of combined diagnosis and therapy with the dual-modality agent. Targeted photo- or acoustic-mediated delivery is also possible.
A microbubble-based imaging/therapeutic agent is introduced. Specifically, gold nanoparticles (AuNRs) are
encapsulated in microbubbles (MBs) for both ultrasound (US) imaging and laser-induced thermotherapy (LIT). In
addition, this agent, AuNR-MB, takes albumin microbubble as a carrier and includes the AuNRs that maintain the
original absorption peak at around 760nm. AuNR-MBs in different sizes are synthesized. Imaging is first performed to
evaluate its feasibility. The enhanced PA and US signals in polyacrylamide gel for in vitro study are measured. The PA
spectroscopy is then performed and the results generally agree with the measured optical absorption although its peak is
slightly broadened and shifted possibly due to mixing. In phantoms, the contrast is 1.531, 2.447, 2.085, 1.994, 0.768, and
0.573 at wavelength of 720, 760, 800, 860, 900, and 940 nm respectively. Finally, the application of the new agent to
LIT is presented. A continuous wave laser at 800 nm is used to heat the samples with the power at 1W. The
photoacoustic (PA) intensity in the region of interest (ROI) is increased by an average of 5.2dB. The increased signal
level implies that the temperature in the ROI can be increased to 44.3°C in aqueous filled setup. Furthermore, the dual-modality
agent has the potential to be used in HIFU therapy, drug delivery and loading of DNA for gene transfer.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
INSTITUTIONAL Select your institution to access the SPIE Digital Library.
PERSONAL Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.