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Nanobubbles can serve as promising, next-generation theranostic platforms for ultrasound (US) and magnetic resonance (MR) imaging, and combined magnetic targeting (MT) and high-intensity focused ultrasound (HIFU)-triggered drug release for tumor therapy. Nanobubble-based dual contrast enhancement agents encapsulated with perfluoropentane and stabilized with superparamagnetic iron oxide (SPIO) nanoparticles have been synthesized through a single-step emulsion process from thermosensitive F127 and polyacrylic acid (PAA). Both US and MR imaging contrast can be optimized by varying the shell thickness and SPIO-embedded concentration. The US contrast can be enhanced from a mean gray value of 62 to 115, and the MR r2 value can be enhanced from 164 to 208 (s(-1)mM (-1)Fe) by increasing the SPIO concentration from 14.1 to 28.2mg/mL, respectively. In vivo investigations of SPIO-embedded nanobubbles in excised tumors under external MT revealed that the US and MR signals change quantitatively compared to the same site without MT. This combined strategy enables the nanobubbles to enhance both passive targeting (increasing the permeability by HIFU) and physical MT of chemotherapeutic drugs to tumors. The integration of functionalities makes this nanobubble system a powerful and viable new tool to achieve simultaneous in vivo tumor imaging and efficacious cancer therapy.

Summary Several biocompatible polymers are capable of large responses to small temperature changes around 37 °C. In water, their responses include shrinkage and swelling as well as transitions in wettability. These properties have been harnessed for biomedical applications such as tissue engineering scaffolds and drug delivery carriers. A soft material/hard material hybrid in which a magnetic metal or oxide is embedded in a temperature-responsive polymer matrix can combine the thermal sensitivity with magnetic signatures. Importantly, nanosizing such construct brings about new desirable features of extremely fast thermal response time, small magnetic hysteresis and enhanced magnetic susceptibility. Remote magnetic maneuvering and heating of the hybrid nanocolloids makes possible such applications as high-throughput enzyme separation and cell screening. Robust drug release on demand may also be obtained using these colloids and nanoparticle-derived thin film devices of combined thermal magnetic sensitivity.

A PVA-based magnetic-sensitive hydrogel (ferrogel) was fabricated by physical cross-linking through a freezing-thawing method. The influence of the constituting components, i.e., Fe3O4 and PVA, on the magnetic-sensitive behavior of the ferrogels was systematically investigated in terms of permeability coefficient (P), partition coefficient (H), space restriction and magnetization. The results show that, the P value in these ferrogels decreases and displays a magnetic sensitivity when it is subjected to magnetic field (MF), which is correlated with the change of H value. In addition, it was found that although the factor of space restriction or magnetization exerts opposite effect on resulting magnetic-sensitive behavior, the superior magnetic-sensitive behavior was observed for the ferrogels with an optimal composition of 17-34% Fe3O4 and 10-12.5% PVA, and can be well correlated with theoretical calculation from the critical parameters of available free volume per nanoparticle (V(free)) and magnetization. A map of magnetic-sensitive behavior was constructed, where a region with relatively stable and highly stimuli-responsive behavior in terms of the concentration of Fe3O4 was observed, however, below or above the "saturation" region (17-34% Fe3O4), a reduction in the magnetic-sensitive behavior was detected. The resulting ferrogels can be engineered with a precise control of the opening and closure of pore configuration, which allows a burst release or no-release action of therapeutically active agent to be controlled externally and magnetically. This suggests that this type of ferrogel can be considered as a class of novel magnetically-tunable drug delivery system.

Magnetic-based scaffolds (ferroscaffolds) were fabricated using an in-situ synthesis of iron oxide nanoparticles in the presence of various concentration of biodegradable gelatin. The resulting ferroscaffolds show an interconnected pore structure with pore sizes ranging from 50 to 200 μm depending on gelatin concentrations. However, the yield of the iron oxide nanoparticles decreases with the increase of gelatin contents, which is due to the presence of polymeric chains that hindered the growth of iron oxide upon co-precipitation. The content of deposited magnetic nanoparticles could reach up to 9.41% and its saturation magnetization ( M s ) was 23.5 emu/g. In addition, while applying a magnetic field (MF), the magnetic interparticles forces immediately formed to reduce the drug release rates in the ferroscaffolds. The ferroscaffolds which possess an excellently magnetic-sensitive behaviors can be potentially used as stimuli-responsive drug carriers and scaffolding materials for tissue engineering.

Novel thermal-sensitive ferrofluids (F127-ferrofluids) consisting of core–shell-type magnetic nanoparticles dispersed in Pluronic F127-containing aqueous solution were prepared. The core (magnet)–shell (Pluronic F127) nanoparticles were synthesized by in situ co-precipitation process, which were characterized using transmission electron microscope, X-ray diffraction and vibrating sample magnetometer. The F127-ferrofluids gelled above the lower critical solution temperatures (LCST) of approximately 23–28 °C, which were higher than that of pure Pluronic F127-fluids (21–25 °C). The increase in the LCST of the F127 ferrofluids may be attributed to a result of a physical interaction between the F127 molecules and the core–shell magnetic nanoparticles.

The magnetic hydrogels were successfully fabricated by chemically cross-linking of gelatin hydrogels and Fe3O4 nanoparticles (ca. 40–60 nm) through genipin (GP) as cross-linking agent. The cross-sectional SEM observation demonstrates that the Fe3O4 nanoparticles were fairly uniformly distributed in the gelatin matrix. Moreover, in vitro release data reveal that drug release profile of the resulting hydrogels is controllable by switching on or off mode of a given magnetic field. While applying magnetic fields to the magnetic hydrogels, the release rate of vitamin B12 of the hydrogels was considerably decreased as compared with those when the field was turned off, suggesting a close configuration of the hydrogels as a result of the aggregation of Fe3O4 nanoparticles. Based on this on-&-off mechanism, the smart magnetic hydrogels based on the gelatin-ferrite hybrid composites can be potentially developed for application in novel drug delivery systems. r 2006 Elsevier B.V. All rights reserved.