Thickness and Sphericity Control of Hollow Hard Silica Shells through Iron (III) Doping: Low Threshold Ultrasound Contrast Agents

Abstract

Silica particles are convenient ultrasound imaging contrast agents because of their long imaging time and ease of modification; however, they require a relatively high insonation power for imaging and have low biodegradability. In this study, 2 µm ultrathin asymmetric hollow silica particles doped with iron (III) (Fe(III)-SiO 2 ) are synthesized to produce biodegradable hard shelled particles with a low acoustic power threshold comparable with commercial soft microbubble contrast agents (Definity) yet with much longer in vivo ultrasound imaging time. Furthermore, high intensity focused ultrasound ablation enhancement with these particles shows a 2.5-fold higher temperature elevation than with Definity at the same applied power. The low power visualization improves utilization of the silica shells as an adjuvant in localized immunotherapy. The data are consistent with asymmetric engineering of hard particle properties that improve functionality of hard versus soft particles.

Dynamic Solid-State Ultrasound Contrast Agent for Monitoring pH Fluctuations In Vivo

“…First, the phantoms containing sUNs at pH 7 were imaged every 24 h over 3 days, confirming a long-term, stable echogenic response (Figure 2a), in comparison to a shorter-lived gas-filled polymer or silica-based microbubbles. 21,25,30,42,43 Next, the sUNs and SiO 2 control phantoms were imaged after incubation in buffer at pH 7, 6, and 5. We observed a 2-fold increase in ultrasound contrast with each decreasing step in pH for the sUNs, while the corresponding signal of the SiO 2 control samples did not change significantly with pH (Figure 2b).…”

“…1–8 μm), which consist of a gaseous core and a phospholipid shell. Microbubbles for applications in molecular imaging is therefore a highly attractive field of research, for both diagnostic and theranostic applications. − However, these microbubbles have a short imaging time window (5–20 min after injection) due to gas diffusion, making them unsuitable for longer-term imaging or in vivo biosensing studies. , In more recent studies regarding contrast agent development, enzymes and inorganic agents have been incorporated into the interior of particles for the diagnostic detection of endogenous levels of hydrogen peroxide in vivo . − Although these ultrasound contrast agents do not suffer from the same fate as conventional ultrasound microbubbles, they are, however, still dose dependent and do not allow for continuous or “on-demand” monitoring.…”

“…Inorganic micro- and nanoparticles have attracted significant attention as echogenic contrast agents, due to their modular material properties (porosity, surface chemistry, etc .) and biocompatibility. ,− Silica can be fabricated into a wide array of sizes and shapes, with different porosities and core/shell structures, and also allows for the incorporation of organic, inorganic, and biological compounds. This versatility enables tuning of the scattering responses in ultrasound imaging through changing the density of the particles and number of interfaces. ,− With the exclusion of solid silica spheres, the silica materials applied in ultrasound imaging to date are dependent on the presence or generation of gas for ultrasound contrast .…”

One-Pot Synthesis of Ternary Alloy Hollow Nanostructures with Controlled Morphologies for Electrocatalysis

“…Designing multimetallic nanostructures has attracted considerable interest because enhanced physical and chemical properties can be derived by maneuvering their structural and compositional characteristics. − Among various multimetallic nanostructures, multimetallic hollow nanostructures (HNSs) have been of particular attention owing to their high surface-to-volume ratio, abundant active sites, and reduced length for both mass and charge transport, which are desirable for potential applications, such as catalysis, sensing, energy storage, and drug delivery. − The complexity of HNSs has been enriched through control over their morphological parameters, such as sphericity, porosity, shell thickness, and the number of shell layers. ,− However, due to difficulties in manipulating the relative reduction kinetics of multiple metal precursors, systematically controlled synthesis of multimetallic HNSs remains a significant challenge.…”