Bubble Inflation Using Phase-Change Perfluorocarbon Nanodroplets as a Strategy for Enhanced Ultrasound Imaging and Therapy
Autor: | Robert F. Mattrey, Jacques Lux, Mark A. Borden, Caroline de Gracia Lux, Carlos J Brambila, Dustin Boyd |
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Rok vydání: | 2020 |
Předmět: |
Materials science
genetic structures Bubble Contrast Media Mice Nude 02 engineering and technology 010402 general chemistry 01 natural sciences Phase change Volume expansion Electrochemistry Animals General Materials Science Particle Size Spectroscopy Ultrasonography Fluorocarbons Microbubbles Surfaces and Interfaces 021001 nanoscience & nanotechnology Condensed Matter Physics 0104 chemical sciences Molecular Weight Ultrasound imaging Nanoparticles Female Volatilization 0210 nano-technology Biomedical engineering |
Zdroj: | Langmuir. 36:2954-2965 |
ISSN: | 1520-5827 0743-7463 |
Popis: | Phase-change perfluorocarbon microdroplets were introduced over 2 decades ago to occlude downstream vessels in vivo. Interest in perfluorocarbon nanodroplets has recently increased to enable extravascular targeting, to rescue the weak ultrasound signal of perfluorocarbon droplets by converting them to microbubbles and to improve ultrasound-based therapy. Despite great scientific interest and advances, applications of phase-change perfluorocarbon agents have not reached clinical testing because of efficacy and safety concerns, some of which remain unexplained. Here, we report that the coexistence of perfluorocarbon droplets and microbubbles in blood, which is inevitable when droplets spontaneously or intentionally vaporize to form microbubbles, is a major contributor to the observed side effects. We develop the theory to explain why the coexistence of droplets and microbubbles results in microbubble inflation induced by perfluorocarbon transfer from droplets to adjacent microbubbles. We also present the experimental data showing up to 6 orders of magnitude microbubble volume expansion, which occludes a 200 μm tubing in the presence of perfluorocarbon nanodroplets. More importantly, we demonstrate that the rate of microbubble inflation and ultimate size can be controlled by manipulating formulation parameters to tailor the agent's design for the potential theranostic application while minimizing the risk to benefit ratio. |
Databáze: | OpenAIRE |
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