Optically and acoustically triggerable sub-micron phase-change contrast agents for enhanced photoacoustic and ultrasound imaging

Abstract

We demonstrate a versatile phase-change sub-micron contrast agent providing three modes of contrast enhancement: 1) photoacoustic imaging contrast, 2) ultrasound contrast with optical activation, and 3) ultrasound contrast with acoustic activation. This agent, which we name ‘Cy-droplet’, has the following novel features. It comprises a highly volatile perfluorocarbon for easy versatile activation, and a near-infrared optically absorbing dye chosen to absorb light at a wavelength with good tissue penetration. It is manufactured via a ‘microbubble condensation’ method. The phase-transition of Cy-droplets can be optically triggered by pulsed-laser illumination, inducing photoacoustic signal and forming stable gas bubbles that are visible with echo-ultrasound in situ. Alternatively, Cy-droplets can be converted to microbubble contrast agents upon acoustic activation with clinical ultrasound. Potentially all modes offer extravascular contrast enhancement because of the sub-micron initial size. Such versatility of acoustic and optical ‘triggerability’ can potentially improve multi-modality imaging, molecularly targeted imaging and controlled drug release.

Dual-mode imaging and therapeutic effects of drug-loaded phase-transition nanoparticles combined with near-infrared laser and low-intensity ultrasound on ovarian cancer

“…After being vaporized via optical irradiation and acoustic pressure, PFC can change its phase and subsequently generate gas (Krafft, 2001 ). And based its phase-shift ability, some studies synthesized PFC-loaded particles to enhance ultrasound images (Lin et al., 2017 ) and PA images (Wilson et al., 2012 ). Furthermore, a photosensitizer and PFC loaded particle can enhance dual mode imaging which combines PA and ultrasound imaging (Hannah et al., 2014 ; Chen et al., 2016 ; Lin, et al., 2017 ).…”

Spatiotemporally controlled nano-sized third harmonic generation agents

“…Likewise, locally triggered disruption of cancer cells may be exploited for release of cancer antigens for immunotherapy [68,69]. Finally, due to high level of interest in applications of PFC nanodroplets in photoacoustic and ultrasound imaging [38,[70][71][72], it is important to have tools that would allow a high resolution longitudinal imaging of PFC nanodroplet activation in biological samples similar to our study presented here.…”

Real‐Time Imaging Tracking of Engineered Macrophages as Ultrasound‐Triggered Cell Bombs for Cancer Treatment

“…The previous evidences showed that PFP can be vaporized into bubbles by heat, light, or ultrasound,33,34 which alters acoustic impedance and enables ultrasonic imaging in real time. To test the ultrasound‐triggered vaporization performance of PFP in DPHs and DPH‐RAWs, we exposed DPHs and DPH‐RAWs to a high‐power ultrasound pulse, numerous bubbles were promptly generated in both DPHs and DPH‐RAWs, which could be clearly observed by an ultrasound imaging system ( Figure a and Movie S1, Supporting Information).…”