Generation of magnetic micrbubbles and their basic magnetic and acoustic mechanism are reviewed. The ultrasound （US） and magnetic resonance （MR） dual imaging, the controlled therapeutic delivery, as well as theranostic multifunctions are all introduced based on recent research results. Some on-going research is also discussed.
There has been unprecedented progress in the development of biomedical nanotechnology and nanoma- terials over the past few decades, and nanoparticle-based drug delivery systems （DDSs） have great potential for clin- ical applications. Among these, magnetic drug delivery systems （MDDSs） based on magnetic nanoparticles （MNPs） are attracting increasing attention owing to their favor- able biocompatibility and excellent multifunctional loading capability. MDDSs primarily have a solid core of super paramagnetic maghemite （y-Fe^03） or magnetite （Fe304） nanoparticles ranging in size from 10 to 100nm. Their surface can be functionalized by organic and/or inorganic modification. Further conjugation with targeting ligands, drug loading, and MNP assembly can provide complex magnetic delivery systems with improved targeting efficacy and reduced toxicity. Owing to their sensitive response to external magnetic fields, MNPs and their assemblies have been developed as novel smart delivery systems. In this review, we first summarize the basic physicochemical and magnetic properties of desirable MDDSs that fulfill the requirements for specific clinical applications. Secondly, we discuss the surface modifications and functionalization issues that arise when designing elaborate MDDSs for future clinical uses. Finally, we highlight recent progress in the design and fabrication of MNPs, magnetic assemblies, and magnetic microbnbbles and liposomes as MDDSs for cancer diagnosis and therapy. Recently, researchers have focused on enhanced targeting efficacy and theranostics by applying step-by-step sequential treatment, and by magnetically mod- ulating dosing regimens, which are the current challenges for clinical applications.
Engineered iron oxide magnetic nanoparticles(MNPs) are one of the most promising tools in nanomedicine-based diagnostics and therapy. However, increasing evidence suggests that their specific delivery efficiency and potential long-term cytotoxicity remain a great concern. In this study, using 12 nm γ-Fe2O3 MNPs, we investigated three types of uptake pathways for MNPs into Hep G2 cells:(1) a conventional incubation endocytic pathway;(2) MNPs co-administrated with microbubbles under ultrasound exposure; and(3) ultrasound delivery of MNPs covalently coated on the surface of microbubbles. The delivery efficiency and intracellular distribution of MNPs were evaluated, and the cytotoxicity induced by reactive oxygen species(ROS) was studied in detail. The results show that MNPs can be delivered into the lysosomes via classical incubation endocytic internalization; however, microbubbles and ultrasound allow the MNPs to pass through the cell membrane and enter the cytosol via a non-internalizing uptake route much more evenly and efficiently. Further, these different delivery routes result in different ROS levels and antioxidant capacities, as well as intracellular glutathione peroxidase activity for Hep G2 cells. Our data indicate that the microbubble–ultrasound treatment method can serve as an efficient cytosolic delivery strategy to minimize long-term cytotoxicity of MNPs.
