The fabrication of novel nanobubble ultrasound contrast agent for potential tumor imaging.

Novel biocompatible nanobubbles were fabricated by ultrasonication of a mixture of Span 60 and polyoxyethylene 40 stearate (PEG40S) followed by differential centrifugation to isolate the relevant subpopulation from the parent suspensions. Particle sizing analysis and optical microscopy inspection indicated that the freshly generated micro/nanobubble suspension was polydisperse and the size distribution was bimodal with large amounts of nanobubbles. To develop a nano-sized contrast agent that is small enough to leak through tumor pores, a fractionation to extract smaller bubbles by variation in the time of centrifugation at 20g (relative centrifuge field, RCF) was suggested. The results showed that the population of nanobubbles with a precisely controlled mean diameter could be sorted from the initial polydisperse suspensions to meet the specified requirements. The isolated bubbles were stable over two weeks under the protection of perfluoropropane gas. The acoustic behavior of the nano-sized contrast agent was evaluated using power Doppler imaging in a normal rabbit model. An excellent power Doppler enhancement was found in vivo renal imaging after intravenous injection of the obtained nanobubbles. Given the broad spectrum of potential clinical applications, the nano-sized contrast agent may provide a versatile adjunct for ultrasonic imaging enhancement and/or treatment of tumors.

Nanoscale Plasticity Behavior of Additive-Manufactured Zirconia-Toughened Alumina Ceramics during Nanoindentation.

The nanoscale plasticity phenomena in zirconia-toughened alumina (ZTA) ceramics with yttria-stabilized zirconia (YSZ) addition of 10% and 30% fabricated by additive manufacturing based on a stereolithography technique were explored in detail by nanoindentation and scanning electron microscopy. It was demonstrated that the initiation of nanoscale plasticity was attributed to the combined contributions from the generation of nanoscale shear deformation bands and localized microcracking at the indentations. Such localized plastic behavior underneath the nanoindenter was interpreted by maximum shear stress analysis. The response of the phase boundary during indentation was emphasized through crack propagation paths, and optimization of alumina-YSZ adaptation through component design and SL processing was expected.

Quantum-dot-modified microbubbles with bi-mode imaging capabilities.

The aim of this paper was to develop a novel bi-mode ultrasound/fluorescent imaging agent through stepwise layer-by-layer deposition of poly(allylamine hydrochloride) (PAH) and CdTe quantum dots (QDs) onto ST68 microbubbles (MBs) produced by sonication of a mixture of surfactants (Span 60 and Tween 80). The experiments using photoluminescence spectroscopy and confocal laser scanning microscopy confirmed that CdTe nanoparticles were successfully adsorbed on the outer surface of the MBs. The static light scattering measurements showed that size distributions of MBs before and after QD deposition met the size requirements for clinical application. The in vitro and in vivo ultrasonography indicated that the QD-modified MBs maintained good contrast enhancement properties as the original MBs. Furthermore, the in vitro ultrasound-targeted microbubble destruction (UTMD) experiment of the QD-MB composites was carried out to validate the ability of MBs to deliver QDs for fluorescent imaging. The results showed that the QD-modified MBs not only maintained the capability of ultrasound imaging, but also could be used as a targeted-drug controlled-release system to deliver the QDs for cell and tissue fluorescent imaging by UTMD. The novel dual-functional imaging agent has potential for a variety of biological and medical applications.

Preparation of polyelectrolyte multilayer coated microbubbles for use as ultrasound contrast agent.

OBJECTIVE: To prepare and characterize polyelectrolyte multilayer film coated microbubbles for use as ultrasound contrast agent (UCA) and evaluate its effects in ultrasonic imaging on normal rabbit's liver parenchyma. METHODS: Perfluorocarbon (PFC)-containing microbubbles (ST68-PFC) were prepared by sonication based on surfactant (Span 60 and Tween 80). Subsequently, the resulting ST68-PFC microbubbles were coated using oppositely charged polyelectrolytes by microbubble-templated layer-by-layer self-assembly technique via electrostatic interaction. The enhancement effects in ultrasonic imaging on normal rabbit's liver parenchyma were assessed. RESULTS: The obtained microbubbles exhibited a narrow size distribution. The polyelectrolytes were successfully assembled onto the surface of ST68-PFC microbubbles. In vivo experiment showed that polyelectrolyte multilayer film coated UCA effectively enhanced the imaging of rabbit's liver parenchyma. CONCLUSIONS: The novel microbubbles UCA coated with polyelectrolyte multilayer, when enabled more function, has no obvious difference in enhancement effects compared with the pre-modified microbubbles. The polymers with chemically active groups (such as amino group and carboxyl group) can be used as the outermost layer for attachment of targeting ligands onto microbubbles, allowing selective targeting of the microbubbles to combine with desired sites.

[Preparation of polyelectrolyte multilayer film-coated microbubble ultrasound contrast agent].

OBJECTIVE: To prepare polyelectrolyte multilayer film-coated microbubble ultrasound contrast agent (UCA) and evaluate its effects in contrast imaging on normal rabbit's liver parenchyma. METHODS: Perfluorocarbon (PFC) -containing microbubble UCA (ST68-PFC) were prepared by sonication-based on surfactants (Span 60 and Tween 80). Subsequently, the resulting ST68-PFC microbubbles were coated using oppositely charged polylysine (PLL) and alginate (Alg) by microbubble-templated layer-by-layer self-assembly technique via electrostatic interaction. The enhancement effects in contrast imaging on normal rabbit's liver parenchyma were assessed. RESULTS: The obtained microbubble UCA exhibited a narrow size distribution. The polyelectrolytes were successfully assembled onto the surface of ST68-PFC microbubbles. In vivo experiment showed that polyelectrolyte multilayer film-coated UCA effectively enhanced the imaging of rabbit's liver parenchyma. CONCLUSIONS: The novel microbubble UCA obtained via layer-by-layer self-assembly, when enabling more functions, has no obvious difference in enhancement effects compared with the premodified microbubbles. The polymers with chemically active groups (such as amino group and carboxyl group) can be used as the outermost layer for the attachment of targeting ligands to microbubbles, which allows the selective targeting of the microbubbles to desired sites.

Novel ultrasound contrast agent based on microbubbles generated from surfactant mixtures of Span 60 and polyoxyethylene 40 stearate.

In this study, novel perfluorocarbon-filled microbubbles as ultrasound contrast agent were fabricated using ultrasonication of a surfactant mixture of sorbitan monostearate (Span 60) and polyoxyethylene 40 stearate (PEG40S) in aqueous media. The microbubbles generated from a 1:9 mixture of PEG40S/Span 60 exhibited an average diameter of 2.08+/-1.27 microm. More than 99% of the microbubbles had a mean particle diameter less than 8 microm, indicating that they were appropriately sized for intravenous administration as ultrasound contrast agent. The stabilization mechanism of the microbubbles was investigated by the Langmuir-Blodgett technique including the measurements of surface pressure-area (pi-A) isotherms and compression-decompression cycles with a two-dimensional monolayer of Span 60 and PEG40S. The dependence on molar fraction of PEG40S in pi-A isotherms of mixed monolayers provided a strong evidence of interactions between the two microbubble-forming materials. It is suggested that the monolayer shell imparts good stability to the microbubbles by three means: (1) a low surface tension monolayer hinders dissolution through the reduction of surface tension, which introduces a mechanical surface pressure that counters the Laplace pressure; (2) the presence of a monolayer shell imparts a significant barrier to gas escaping from the core into the aqueous medium; and (3) encapsulation elasticity stabilizes microbubbles against diffusion-driven dissolution and explains the long shelf-life of microbubble contrast agent. The preliminary in vivo ultrasound imaging study showed that such stabilized microbubbles demonstrated excellent enhancement under grey-scale pulse inversion harmonic imaging and power Doppler imaging.