Yuanzhe Piao

Nanotechnology offers tremendous potential for future biomedical technology. Due to their unique characteristics including superparamagnetic or fluorescent properties, and small size comparable to biomolecules, nanostructured materials have emerged as novel bioimaging, diagnostic, and therapeutic agents for the future medical field. Especially, the combinations of various nanostructured materials with different properties can offer synergetic multifunctional nanomedical platforms, which make it possible to accomplish multimodal imaging, and simultaneous diagnosis and therapy. Moreover, the conjugation of targeting moieties on the surface of these multifunctional nanomaterials gives them specific targeted imaging and therapeutic properties. In this tutorial review, we will summarize the recent reports on the fabrication strategies of multifunctional nanoplatforms and their applications to targeted multimodal imaging and simultaneous diagnosis and therapy.

We studied the kinetics of the formation of iron oxide nanocrystals obtained from the solution-phase thermal decomposition of iron-oleate complex via the "heating-up" process. To obtain detailed information on the thermal decomposition process and the formation of iron oxide nanocrystals in the solution, we performed a thermogravimetric-mass spectrometric analysis (TG-MS) and in-situ magnetic measurements using SQUID. The TG-MS results showed that iron-oleate complex was decomposed at around 320 degrees C. The in-situ SQUID data revealed that the thermal decomposition of iron-oleate complex generates intermediate species, which seem to act as monomers for the iron oxide nanocrystals. Extensive studies on the nucleation and growth process using size exclusion chromatography, the crystallization yield data, and TEM showed that the sudden increase in the number concentration of the nanocrystals (burst of nucleation) is followed by the rapid narrowing of the size distribution (size focusing). We constructed a theoretical model to describe the "heating-up" process and performed a numerical simulation. The simulation results matched well with the experimental data, and furthermore they are well fitted to the well-known LaMer model that is characterized by the burst of nucleation and the separation of nucleation and growth under continuous monomer supply condition. Through this theoretical work, we showed that the "heating-up" and "hot injection" processes could be understood within the same theoretical framework in which they share the characteristics of nucleation and growth stages.

Suitably integrating multiple nanomaterials into nanostructured particle systems with specific combinations of properties has recently attracted significant attention in the research community. In particular, numerous particle systems have been designed and fabricated by integrating diverse materials with monodispersed silica nanoparticles. One or more distinct nanomaterials can be assembled on, encapsulated within, or integrated both inside and on the surface of silica nanoparticles using different chemistries and techniques to create multifunctional nanosystems. Research on these particle systems for biomedical applications has progressed rapidly during recent years due to the synergistic advantages of these complexes compared to the use of single components. This feature article surveys recent research progress on the fabrication strategies of these nanoparticle systems and their applications to medical diagnostics and therapy, thereby paving the way for the emerging field of nanomedicine.

Ever since Au nanoparticles were developed as X-ray contrast agents, researchers have actively sought alternative nanoparticle-based imaging probes that are not only inexpensive but also safe for clinical use. Herein, we demonstrate that bioinert tantalum oxide nanoparticles are suitable nanoprobes for high-performance X-ray computed tomography (CT) imaging while simultaneously being cost-effective and meeting the criteria as a biomedical platform. Uniformly sized tantalum oxide nanoparticles were prepared using a microemulsion method, and their surfaces were readily modified using various silane derivatives through simple in situ sol-gel reaction. The silane-modified surface enabled facile immobilization of functional moieties such as polyethylene glycol (PEG) and fluorescent dye. PEG was introduced to endow the nanoparticles with biocompatibility and antifouling activity, whereas immobilized fluorescent dye molecules enabled simultaneous fluorescence imaging as well as X-ray CT imaging. The resulting nanoparticles exhibited remarkable performances in the in vivo X-ray CT angiography and bimodal image-guided lymph node mapping. We also performed an extensive study on in vivo toxicity of tantalum oxide nanoparticles, revealing that the nanoparticles did not affect normal functioning of organs.