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With the aim of obtaining a carrier for combined magnetic‐field‐ and ultrasound‐targeted nucleic acid delivery, acoustically active lipospheres are prepared that comprise magnetic nanoparticles and plasmid DNA or synthetic siRNA. The lipospheres, with average diameters of 5 μm and smaller, are obtained upon shaking a mixture of soybean oil, a cationic lipid, magnetic nanoparticles, a nucleic acid, and aqueous buffer in a perfluoropropane atmosphere in a sealed vial. These lipospheres create contrast in ultrasound imaging and display greatly increased magnetophoretic mobility and in consequence greatly improved magnetic retention in a flow model when compared with free magnetic nanoparticles. In cell culture, the lipospheres are sedimented within minutes to the surface of cells using a gradient magnetic field. This sedimentation results in the association of about 50% of the applied plasmid DNA with the cells and in functional DNA and siRNA delivery in vitro. Under these conditions, ultrasound does not have an enhancing effect on nucleic acid delivery. When magnetic, acoustically active lipospheres carrying 125iodine‐labeled plasmid DNA are injected into the tail veins of mice, the application of a gradient magnetic field to the chests of the mice results in a two‐ to threefold enrichment of both lung lobes with the plasmid. A similar enrichment is obtained when ultrasound alone (1 MHz, 10 min) is applied. The combined application of magnetic field and ultrasound has no synergistic effect in terms of liposphere capture in the lungs. Histological analysis reveals intact lipospheres in lung capillaries. A synergistic effect of magnetic field and ultrasound is observed in site‐specific plasmid deposition in a dorsal skinfold chamber model in mice after injection into the carotis. These conditions also result in functional plasmid delivery to the vasculature after intrajugular injection.

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Interleukin‐8 (IL‐8), a 72 amino acid peptide secreted by cells of the immune system and of the amnion, chorion and decidua, was measured in women in late pregnancy. IL‐8 was detected in the urine of 91 of 104 women with premature rupture of the fetal membranes, with values exceeding 1000 ng/L in cases of severe intra‐amniotic infection. Women with urinary tract infections were excluded. The routine measurement of IL‐8 in urine, together with C‐reactive protein in serum, thus provides a low risk and technically simple approach to the assessment of intra‐amniotic infection.

Photoacoustic imaging combines the resolution of ultrasound imaging with the contrast of optical imaging, while maintaining a penetration depth up to a few centimeters. Inorganic gold nanorods can be employed as photoacoustic contrast agents. However, the toxicological properties of such nanoparticles are still under investigation. At the same time, there is an increasing need for clinically established photoacoustic contrast agents. In this paper, therefore, we investigate the photoacoustic properties of Ferucarbotran, which is a clinically established nanoscale contrast agent for magnetic resonance imaging. Gelatin phantoms containing cubes with different gelatin-Ferucarbotran mixture concentrations were prepared and irradiated by a Nd:YAG laser (1064 nm). First, the photoacoustic signals were acquired by a single element ultrasound transducer (7.5 MHz) and evaluated quantitatively. In a second setup, photoacoustic imaging of Ferucarbotran with a modified clinical scanner was demonstrated. The experiments showed that in order to achieve a 6 dB gain of received photoacoustic signal energy, compared to the sensitivity threshold of the used system, a Ferucarbotran concentration of 1.9 micromol Fe/ml is needed. The photoacoustic imaging was successful and showed a contrast-to-background ratio of 15.7 dB for a concentration of 11.63 micromol Fe/ml. However, for imaging in tissue the signal-to-noise ratio has to be increased.

Sonoporation is the ultrasound induced transient opening of cell membranes. Large scale oscillation of nearby microbubbles (MBs) is considered to be the primary effect in sonoporation whereas MB destruction correlates with lower sonoporation efficiency and increased cell damage. The scale of MB oscillation in a cloud can be determined by monitoring subharmonic emission. In this study, SW480 cells are grown in Opticell containers, which are filled with a growth medium containing SonoVue MBs and propidium iodide (PI). Each container is placed in water in the focus of a single element transducer emitting 10 cycles sine-bursts at 3.3 MHz. The peak negative pressure is varied from 75 to 750 kPa. Scattered signals are recorded by a broadband transducer to monitor subharmonic-to-fundamental ratio (SFR) during therapy. A fluorescence microscope is focused on the therapy region to monitor PI fluorescence during and after acoustic excitation. PI cannot overcome intact cell membranes and changes its fluorescence properties when bound to intracellular fluid. A cell is considered sonoporated, if it reveals a sharp rise of fluorescence intensity and a subsequent decrease. A cell is considered permanently stained, if fluorescence intensity is concentrated at the cell nucleus and rises to a plateau. For maximum peak negative excitation pressure, maximum sonoporation (4.9%) and maximum permanent poration (2.8%) is observed. Correcting the number of sonoporated cells by the number of permanently stained cells, best sonoporation efficiency is achieved for the amplitude of 520 kPa. The same holds for the SFR, which significantly rises to a maximum of -26,6 dB at 520 kPa, too. The relationship of sonoporation efficiency and SFR reveals that subharmonic emission from ultrasound contrast agent is an indicator for sonoporation efficiency of cell monolayers.