India Ink Incorporated Multifunctional Phase-transition Nanodroplets for Photoacoustic/Ultrasound Dual-modality Imaging and Photoacoustic Effect Based Tumor Therapy

Abstract

The in vivo applications of gas-core microbubbles have been limited by gas diffusion, rapid body clearance, and poor vascular permeability. To overcome these limitations, using a modified three-step emulsion process, we have developed a first-of-its-kind India ink incorporated optically-triggerable phase-transition perfluorocarbon nanodroplets (INDs) that can provide not only three types of contrast mechanisms—conventional/thermoelastic photoacoustic, phase-transition/nonlinear photoacoustic, and ultrasound imaging contrasts, but also a new avenue for photoacoustic effect mediated tumor therapy. Upon pulsed laser illumination above a relatively low energy threshold, liquid-gas phase transition of the INDs has been demonstrated both in vitro and in vivo, offering excellent contrasts for photoacoustic and ultrasound dual-modality imaging. With further increased laser energy, the nanodroplets have been shown to be capable of destructing cancer cells in vivo, presumably due to the photoacoustic effect induced shock-wave generation from the carbon particles of the incorporated India ink. The demonstrated results suggest that the developed multifunctional phase-transition nanodroplets have a great potential for many theranostic biomedical applications, including photoacoustic/ultrasound dual-modality molecular imaging and targeted, localized cancer therapy.

Magnetic nanoparticle-promoted droplet vaporization for in vivo stimuli-responsive cancer theranostics

“…Biocompatible metal NPs are generally employed to convert photons into thermal energy and induce the evaporation of liquid droplets. [21][22][23] The shallow penetration depth of the laser, however, substantially hinders its further clinical translation. It is noted that both ADV and ODV require a pre-determined tumor position to accomplish site-specific phase transformation for imaging and therapy, which means that these two modalities cannot intrinsically overcome the drawbacks of particle sizes of CAs or SAs for early diagnosis and efficient therapy of cancer.…”

Engineering optically triggered droplets for photoacoustic imaging and therapy

“…More recently, phase change agents have been proposed as promising photoacoustic contrast agents [7][8][9][10][11][12][13]. In this case, PFC droplets are designed to absorb light at the wavelength of interest by incorporating a light absorbing species within the droplet or on the periphery.…”

Oxygen and indocyanine green loaded phase-transition nanoparticle-mediated photo-sonodynamic cytotoxic effects on rheumatoid arthritis fibroblast-like synoviocytes

“…In recent years, poly(dllactide-co-glycolic acid [PLGA]) has been widely used in medical and biologic applications for its biodegradability, biocompatibility, safety, and stability. [29][30][31][32] Several studies have demonstrated that ICG-loaded PLGA nanoparticles (NPs) could improve the stability of ICG and act as an efficient carrier to deliver ICG to the lesion area to perform the function of therapy or imaging. [33][34][35][36] Furthermore, it has been demonstrated that liquid perfluorocarbon compounds (PFC) act as a good oxygen carrier 37 and are widely used in ultrasound imaging, and PLGA NPs entrapped with PFC droplets have been reported in several studies.…”