ICUS Weekly News Monitor 8-18-2016

1.  Dove Medical Press,  Aug 12,2016,  Diagnosis of prostate cancer using anti-PSMA aptamer A10-3.2-oriented lipid nanobubbles      Authors:  Xiaozhou Fan, et al
 
2.  Science Daily,  Aug 9, 2016,  Researchers immobilize underwater bubbles
Source: American Institute of Physics, Authors: Zoubida Hammadi, et al
 
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Dove Medical Press
Volume 2016:11 Pages 3939—3950
DOI https://dx.doi.org/10.2147/IJN.S112951
Aug 12,2016
 
Diagnosis of prostate cancer using anti-PSMA aptamer A10-3.2-oriented lipid nanobubbles
 
Authors:  Xiaozhou Fan,1 Yanli Guo,1 Luofu Wang,2 Xingyu Xiong,1 Lianhua Zhu,1 Kejing Fang1
1Department of Ultrasound, Southwest Hospital, Third Military Medical University, Chongqing, People’s Republic of China; 2Department of Urology, Daping Hospital, Institute of Surgery Research, Third Military Medical University, Chongqing, People’s Republic of China
 
Abstract:
In this study, the lipid targeted nanobubble carrying the A10-3.2 aptamer against prostate specific membrane antigen was fabricated, and its effect in the ultrasound imaging of prostate cancer was investigated. Materials including 2-dipalmitoyl-sn-glycero-3-phosphocholine, 1,2-dipalmitoyl-sn-glycero-3-phosphatidic acid, 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine, 1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol, carboxyl-modified 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, and polyethyleneglycol-2000 were for mechanical oscillation, and nanobubbles were obtained through the centrifugal flotation method. After mice were injected with nanobubbles, abdominal color Doppler blood flow imaging significantly improved. Through left ventricular perfusion with normal saline to empty the circulating nanobubbles, nanobubbles still existed in tumor tissue sections, which demonstrated that nanobubbles could enter tissue spaces via the permeability and retention effect. Fluorinated A10-3.2 aptamers obtained by chemical synthesis had good specificity for PSMA-positive cells, and were linked with carboxyl-modified 1,2-distearoyl-sn-glycero-3-phosphoethanolamine lipid molecules from the outer shell of nanobubbles via amide reaction to construct targeted nanobubbles. Gel electrophoresis and immunofluorescence confirmed that targeted nanobubbles were fabricated successfully. Next, targeted nanobubbles could bind with PSMA-positive cells (C4-2 cells), while not with PSMA-negative cells (PC-3 cells), using in vitro binding experiments and flow cytometry at the cellular level. Finally, C4-2 and PC-3 xenografts in mice were used to observe changes in parameters of targeted and non-targeted nanobubbles in the contrast-enhanced ultrasound mode, and the distribution of Cy5.5-labeled targeted nanobubbles in fluorescent imaging of live small animals. Comparison of ultrasound indicators between targeted and non-targeted nanobubbles in C4-2 xenografts showed that they had similar peak times (P>0.05), while the peak intensity, half time of peak intensity, and area under the curve of ½ peak intensity were significantly different (P<0.05). In PC-3 xenografts, there were no differences in these four indicators. Fluorescent imaging indicated that targeted nanobubbles had an aggregation ability in C4-2 xenograft tumors. In conclusion, targeted nanobubbles carrying the anti-PSMA A10-3.2 aptamer have a targeted imaging effect in prostate cancer.
 
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Science Daily
Aug 9, 2016
 
Researchers immobilize underwater bubbles
New technique to 'freeze' newly created microbubbles in their tracks could lead to new applications in medicine and the nuclear industry
 
Source: American Institute of Physics
Authors: Zoubida Hammadi, Laurent Lapena, Roger Morin, Juan Olives.
Immobilization of a bubble in water by nanoelectrolysis;  Applied Physics Letters, 2016; 109 (6): 064101 DOI: 10.1063/1.4960098
 
Controlling bubbles is a difficult process and one that many of us experienced in a simplistic form as young children wielding a bubble wand, trying to create bigger bubbles without popping them. A research team in CINaM-CNRS Aix-Marseille Université in France has turned child's play into serious business.
 
They demonstrated they could immobilize a microbubble created from water electrolysis as if the Archimedes' buoyant force that would normally push it to the surface didn't exist. This new and surprising phenomenon described this week in Applied Physics Letters, from AIP Publishing, could lead to applications in medicine, the nuclear industry or micromanipulation technology.
 
While bubbles are observed frequently in nature, it is not easy to control their diameter, position or time of formation. Previous work by the French research team explored how to control the hydrogen and oxygen gas bubbles formed by the breakdown of water using electricity. They showed that if one of the electrodes is tip-shaped -- with a curvature radius at its apex ranging from 1 nanometer to 1 micrometer -- and an alternating electric current with defnite values of amplitude and frequency was used, microbubbles could be produced at a single point at the apex of the nanoelectrode.
 
In the current work, the team has demonstrated a new and surprising phenomenon: the immobilization of a single microbubble in water. After a bubble is produced (at the apex of the nanoelectrode), it is immobilized by rapidly increasing the frequency of the electric current. It is a stable situation: No matter which direction the electrode moves, the bubble remains above and at the same distance from the electrode.
 
The scientists propose that the hydrogen or oxygen molecules enter the immobilized bubble through the lower surface and exit the bubble through the upper surface. The gas molecules are only produced at a single point at the apex of the nanoelectrode.
 
The team from CINaM-CNRS worked with researchers in acoustics who use ultrasounds for the detection and the characterization of microbubbles. They needed highly calibrated bubbles and the team proposed producing such bubbles using water electrolysis. The team incorporated a number of new ideas and methods in their approach. "While it is usual to consider that electrolysis is controlled by the electric potential, we show that the fundamental quantity is in fact the electric field which is why we use a tip-shaped electrode with a very small curvature radius at the apex," said Juan Olives, a member of the research team. The use of an alternating current of sufficient frequency then produces "nanoelectrolysis," which is the nanolocalization of the electrolysis reactions at a single point.
 
The greatest surprise in the findings was that, although nothing seems to move when you observe the experiment, in fact, all is moving in an apparent steady state, Olives said. Hydrogen and oxygen molecules are continually produced at the apex of the nanoelectrode, they move in the solution and in the bubble, they enter and leave the bubble, and there is a convection velocity in the solution and in the bubble. Everything is moving, except the surface of the bubble, Olives said.
 
Controlling microbubbles is critical to numerous applications in medicine including as ultrasound contrast agents, for breaking up blood clots, and for gas embolotherapy, which is the intentional blocking of an artery to prevent excessive blood loss. Controlling microbubbles is also important in the nuclear industry, where microbubbles in liquid sodium coolant can cause problems.

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