Dokyoon Kim

Synthesis of Uniform Ferrimagnetic Magnetite Nanocubes

We synthesized uniform ferrimagnetic magnetite nanocubes in the size range from 20 to 160 nm. The magnetic property of the nanocubes was characterized, and magnetic separation of the histidine-tagged protein was demonstrated.

Synthesis of Uniform Hollow Oxide Nanoparticles through Nanoscale Acid Etching

We synthesized various hollow oxide nanoparticles from as-prepared MnO and iron oxide nanocrystals. Heating metal oxide nanocrystals dispersed in technical grade trioctylphosphine oxide (TOPO) at 300 degrees C for hours yielded hollow nanoparticles retaining the size and shape uniformity of the original nanocrystals. The method was highly reproducible and could be generalized to synthesize hollow oxide nanoparticles of various sizes, shapes, and compositions. Control experiments revealed that the impurities in technical grade TOPO, especially alkylphosphonic acid, were responsible for the etching of metal oxide nanocrystals to the hollow structures. Elemental mapping analysis revealed that the inward diffusion of phosphorus and the outward diffusion of metal took place in the intermediate stages during the etching process. The elemental analysis using XPS, EELS, and EDX showed that the hollow nanoparticles were amorphous metal oxides containing significant amount of phosphorus. The hollow nanoparticles synthesized from MnO and iron oxide nanocrystals were paramagnetic at room temperature and when dispersed in water showed spin relaxation enhancement effect for magnetic resonance imaging (MRI). Because of their morphology and magnetic property, the hollow nanoparticles would be utilized for multifunctional biomedical applications such as the drug delivery vehicles and the MRI contrast agents.

Magnetosome-like ferrimagnetic iron oxide nanocubes for highly sensitive MRI of single cells and transplanted pancreatic islets

For ultrasensitive magnetic resonance imaging (MRI), magnetic nanoparticles with extremely high r2 relaxivity are strongly desired. Magnetosome-like nanoparticles were prepared by coating polyethylene glycol-phospholipid (PEG-phospholipid) onto ferrimagnetic iron oxide nanocubes (FIONs). FIONs exhibited a very high relaxivity (r2) of 324 mM-1 s-1, allowing efficient labeling of various kinds of cells. The magnetic resonance (MR) imaging of single cells labeled with FIONs is demonstrated not only in vitro but also in vivo. Pancreatic islet grafts and their rejection could be imaged using FIONs on a 1.5 T clinical MRI scanner. The strong contrast effect of FIONs enabled MR imaging of transplanted islets in small rodents as well as in large animals. Therefore, we expect that MR imaging of pancreatic islet grafts using FIONs has the potentials for clinical applications. Furthermore, FIONs will enable highly sensitive noninvasive assessment after cell transplantation.

Mitochondria-Targeting Ceria Nanoparticles as Antioxidants for Alzheimer's Disease

Mitochondrial oxidative stress is a key pathologic factor in neurodegenerative diseases, including Alzheimers disease. Abnormal generation of reactive oxygen species (ROS), resulting from mitochondrial dysfunction, can lead to neuronal cell death. Ceria (CeO2) nanoparticles are known to function as strong and recyclable ROS scavengers by shuttling between Ce(3+) and Ce(4+) oxidation states. Consequently, targeting ceria nanoparticles selectively to mitochondria might be a promising therapeutic approach for neurodegenerative diseases. Here, we report the design and synthesis of triphenylphosphonium-conjugated ceria nanoparticles that localize to mitochondria and suppress neuronal death in a 5XFAD transgenic Alzheimers disease mouse model. The triphenylphosphonium-conjugated ceria nanoparticles mitigate reactive gliosis and morphological mitochondria damage observed in these mice. Altogether, our data indicate that the triphenylphosphonium-conjugated ceria nanoparticles are a potential therapeutic candidate for mitochondrial oxidative stress in Alzheimers disease.

Continuous O2-Evolving MnFe2O4 Nanoparticle-Anchored Mesoporous Silica Nanoparticles for Efficient Photodynamic Therapy in Hypoxic Cancer

Therapeutic effects of photodynamic therapy (PDT) are limited by cancer hypoxia because the PDT process is dependent on O2 concentration. Herein, we design biocompatible manganese ferrite nanoparticle-anchored mesoporous silica nanoparticles (MFMSNs) to overcome hypoxia, consequently enhancing the therapeutic efficiency of PDT. By exploiting the continuous O2-evolving property of MnFe2O4 nanoparticles through the Fenton reaction, MFMSNs relieve hypoxic condition using a small amount of nanoparticles and improve therapeutic outcomes of PDT for tumors in vivo. In addition, MFMSNs exhibit T2 contrast effect in magnetic resonance imaging (MRI), allowing in vivo tracking of MFMSNs. These findings demonstrate great potential of MFMSNs for theranostic agents in cancer therapy.

Recent Advances in Inorganic Nanoparticle-Based NIR Luminescence Imaging: Semiconductor Nanoparticles and Lanthanide Nanoparticles

Several types of nanoparticle-based imaging probes have been developed to replace conventional luminescent probes. For luminescence imaging, near-infrared (NIR) probes are useful in that they allow deep tissue penetration and high spatial resolution as a result of reduced light absorption/scattering and negligible autofluorescence in biological media. They rely on either an anti-Stokes or a Stokes shift process to generate luminescence. For example, transition metal-doped semiconductor nanoparticles and lanthanide-doped inorganic nanoparticles have been demonstrated as anti-Stokes shift-based agents that absorb NIR light through two- or three-photon absorption process and upconversion process, respectively. On the other hand, quantum dots (QDs) and lanthanide-doped nanoparticles that emit in NIR-II range (∼1000 to ∼1350 nm) were suggested as promising Stokes shift-based imaging agents. In this topical review, we summarize and discuss the recent progress in the development of inorganic nanoparticle-based luminescence imaging probes working in NIR range.

Ceria–Zirconia Nanoparticles as an Enhanced Multi‐Antioxidant for Sepsis Treatment

The two oxidation states of ceria nanoparticles, Ce3+ and Ce4+ , play a pivotal role in scavenging reactive oxygen species (ROS). In particular, Ce3+ is largely responsible for removing O2- and . OH that are associated with inflammatory response and cell death. The synthesis is reported of 2 nm ceria-zirconia nanoparticles (CZ NPs) that possess a higher Ce3+ /Ce4+ ratio and faster conversion from Ce4+ to Ce3+ than those exhibited by ceria nanoparticles. The obtained Ce0.7 Zr0.3 O2 (7CZ) NPs greatly improve ROS scavenging performance, thus regulating inflammatory cells in a very low dose. Moreover, 7CZ NPs are demonstrated to be effective in reducing mortality and systemic inflammation in two representative sepsis models. These findings suggest that 7CZ NPs have the potential as a therapeutic nanomedicine for treating ROS-related inflammatory diseases.

Renal-Clearable Hollow Bismuth Subcarbonate Nanotubes for Tumor Targeted Computed Tomography Imaging and Chemoradiotherapy

Although metallic nanomaterials with high X-ray attenuation coefficients have been widely used as X-ray computed tomography (CT) contrast agents, their intrinsically poor biodegradability requires them to be cleared from the body to avoid any potential toxicity. On the other hand, extremely small-sized nanomaterials with outstanding renal clearance properties are not much effective for tumor targeting because of their too rapid clearance in vivo. To overcome this dilemma, here we report on the hollow bismuth subcarbonate nanotubes (BNTs) assembled from renal-clearable ultrasmall bismuth subcarbonate nanoclusters for tumor-targeted imaging and chemoradiotherapy. The BNTs could be targeted to tumors with high efficiency and exhibit a high CT contrast effect. Moreover, simultaneous radio- and chemotherapy using drug-loaded BNTs could significantly suppress tumor volumes, highlighting their potential application in CT imaging-guided therapy. Importantly, the elongated nanotubes could be disassembled into isolated small nanoclusters in the acidic tumor microenvironment, accelerating the payload release and kidney excretion. Such body clearable CT contrast agent with high imaging performance and multiple therapeutic functions shall have a substantial potential for biomedical applications.

Multifunctional nanoparticles as a tissue adhesive and an injectable marker for image-guided procedures.

Tissue adhesives have emerged as an alternative to sutures and staples for wound closure and reconnection of injured tissues after surgery or trauma. Owing to their convenience and effectiveness, these adhesives have received growing attention particularly in minimally invasive procedures. For safe and accurate applications, tissue adhesives should be detectable via clinical imaging modalities and be highly biocompatible for intracorporeal procedures. However, few adhesives meet all these requirements. Herein, we show that biocompatible tantalum oxide/silica core/shell nanoparticles (TSNs) exhibit not only high contrast effects for real-time imaging but also strong adhesive properties. Furthermore, the biocompatible TSNs cause much less cellular toxicity and less inflammation than a clinically used, imageable tissue adhesive (that is, a mixture of cyanoacrylate and Lipiodol). Because of their multifunctional imaging and adhesive property, the TSNs are successfully applied as a hemostatic adhesive for minimally invasive procedures and as an immobilized marker for image-guided procedures.

Device-assisted transdermal drug delivery

&NA; Transdermal drug delivery is a prospective drug delivery strategy to complement the limitations of conventional drug delivery systems including oral and injectable methods. This delivery route allows both convenient and painless drug delivery and a sustained release profile with reduced side effects. However, physiological barriers in the skin undermine the delivery efficiency of conventional patches, limiting drug candidates to small‐molecules and lipophilic drugs. Recently, transdermal drug delivery technology has advanced from unsophisticated methods simply relying on natural diffusion to drug releasing systems that dynamically respond to external stimuli. Furthermore, physical barriers in the skin have been overcome using microneedles, and controlled delivery by wearable biosensors has been enabled ultimately. In this review, we classify the evolution of advanced drug delivery strategies based on generations and provide a comprehensive overview. Finally, the recent progress in advanced diagnosis and therapy through customized drug delivery systems based on real‐time analysis of physiological cues is highlighted. Graphical abstract Figure. No caption available.