Kwangsoo Shin

Large-Scale Synthesis of Uniform and Extremely Small-Sized Iron Oxide Nanoparticles for High-Resolution T1 Magnetic Resonance Imaging Contrast Agents

Uniform and extremely small-sized iron oxide nanoparticles (ESIONs) of < 4 nm were synthesized via the thermal decomposition of iron-oleate complex in the presence of oleyl alcohol. Oleyl alcohol lowered the reaction temperature by reducing iron-oleate complex, resulting in the production of small-sized nanoparticles. XRD pattern of 3 nm-sized nanoparticles revealed maghemite crystal structure. These nanoparticles exhibited very low magnetization derived from the spin-canting effect. The hydrophobic nanoparticles can be easily transformed to water-dispersible and biocompatible nanoparticles by capping with the poly(ethylene glycol)-derivatized phosphine oxide (PO-PEG) ligands. Toxic response was not observed with Fe concentration up to 100 μg/mL in MTT cell proliferation assay of POPEG-capped 3 nm-sized iron oxide nanoparticles. The 3 nm-sized nanoparticles exhibited a high r(1) relaxivity of 4.78 mM(-1) s(-1) and low r(2)/r(1) ratio of 6.12, demonstrating that ESIONs can be efficient T(1) contrast agents. The high r(1) relaxivities of ESIONs can be attributed to the large number of surface Fe(3+) ions with 5 unpaired valence electrons. In the in vivo T(1)-weighted magnetic resonance imaging (MRI), ESIONs showed longer circulation time than the clinically used gadolinium complex-based contrast agent, enabling high-resolution imaging. High-resolution blood pool MR imaging using ESIONs enabled clear observation of various blood vessels with sizes down to 0.2 mm. These results demonstrate the potential of ESIONs as T(1) MRI contrast agents in clinical settings.

Self-assembled Fe3O4 nanoparticle clusters as high-performance anodes for lithium ion batteries via geometric confinement.

Although different kinds of metal oxide nanoparticles continue to be proposed as anode materials for lithium ion batteries (LIBs), their cycle life and power density are still not suitable for commercial applications. Metal oxide nanoparticles have a large storage capacity, but they suffer from the excessive generation of solid-electrolyte interphase (SEI) on the surface, low electrical conductivity, and mechanical degradation and pulverization resulted from severe volume expansion during cycling. Herein we present the preparation of mesoporous iron oxide nanoparticle clusters (MIONCs) by a bottom-up self-assembly approach and demonstrate that they exhibit excellent cyclic stability and rate capability derived from their three-dimensional mesoporous nanostructure. By controlling the geometric configuration, we can achieve stable interfaces between the electrolyte and active materials, resulting in SEI formation confined on the outer surface of the MIONCs.

Multifunctional Fe3O4/TaOx Core/Shell Nanoparticles for Simultaneous Magnetic Resonance Imaging and X-ray Computed Tomography

Multimodal imaging is highly desirable for accurate diagnosis because it can provide complementary information from each imaging modality. In this study, a sol-gel reaction of tantalum(V) ethoxide in a microemulsion containing Fe(3)O(4) nanoparticles (NPs) was used to synthesize multifunctional Fe(3)O(4)/TaO(x) core/shell NPs, which were biocompatible and exhibited a prolonged circulation time. When the NPs were intravenously injected, the tumor-associated vessel was observed using computed tomography (CT), and magnetic resonance imaging (MRI) revealed the high and low vascular regions of the tumor.

High-resolution three-photon biomedical imaging using doped ZnS nanocrystals

Three-photon excitation is a process that occurs when three photons are simultaneously absorbed within a luminophore for photo-excitation through virtual states. Although the imaging application of this process was proposed decades ago, three-photon biomedical imaging has not been realized yet owing to its intrinsic low quantum efficiency. We herein report on high-resolution in vitro and in vivo imaging by combining three-photon excitation of ZnS nanocrystals and visible emission from Mn(2+) dopants. The large three-photon cross-section of the nanocrystals enabled targeted cellular imaging under high spatial resolution, approaching the theoretical limit of three-photon excitation. Owing to the enhanced Stokes shift achieved through nanocrystal doping, the three-photon process was successfully applied to high-resolution in vivo tumour-targeted imaging. Furthermore, the biocompatibility of ZnS nanocrystals offers great potential for clinical applications of three-photon imaging.

Wearable/disposable sweat-based glucose monitoring device with multistage transdermal drug delivery module

A sweat-based glucose monitoring device with transdermal drug delivery is developed for noninvasive diabetes treatment. Electrochemical analysis of sweat using soft bioelectronics on human skin provides a new route for noninvasive glucose monitoring without painful blood collection. However, sweat-based glucose sensing still faces many challenges, such as difficulty in sweat collection, activity variation of glucose oxidase due to lactic acid secretion and ambient temperature changes, and delamination of the enzyme when exposed to mechanical friction and skin deformation. Precise point-of-care therapy in response to the measured glucose levels is still very challenging. We present a wearable/disposable sweat-based glucose monitoring device integrated with a feedback transdermal drug delivery module. Careful multilayer patch design and miniaturization of sensors increase the efficiency of the sweat collection and sensing process. Multimodal glucose sensing, as well as its real-time correction based on pH, temperature, and humidity measurements, maximizes the accuracy of the sensing. The minimal layout design of the same sensors also enables a strip-type disposable device. Drugs for the feedback transdermal therapy are loaded on two different temperature-responsive phase change nanoparticles. These nanoparticles are embedded in hyaluronic acid hydrogel microneedles, which are additionally coated with phase change materials. This enables multistage, spatially patterned, and precisely controlled drug release in response to the patient’s glucose level. The system provides a novel closed-loop solution for the noninvasive sweat-based management of diabetes mellitus.

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.

Electromechanical cardioplasty using a wrapped elasto-conductive epicardial mesh

A mesh made of a conductive nanowire composite can be wrapped around the heart to improve hemodynamics in experimental heart failure in rodents. An electromechanical hug for the heart Heart failure can be treated by pacemakers to keep the beats in rhythm, but pacemakers apply electrical stimulation at specific points and do not provide comprehensive coverage of the entire organ. Park and colleagues therefore devised an electric mesh that wraps around the heart to deliver electrical impulses to the whole ventricular myocardium. The heart wrap was made from silver nanowires embedded in a rubber polymer that could conform to the unique three-dimensional anatomy of different hearts. In rats that had a heart attack, the mesh integrated structurally and electrically with the myocardium and exerted beneficial effects, including preserved diastolic relaxation, reduced wall stress, and improved cardiac contractile function. The mesh also terminated induced ventricular arrhythmia, acting as an epicardial defibrillator. Such epicardial meshes have been tested in clinical trials before and were effective in preventing ventricular remodeling but showed controversial results in long-term survival. The authors hope that their device, which is designed to integrate more faithfully with the heart’s structure and electrical conduction system, is more consistent in people. Heart failure remains a major public health concern with a 5-year mortality rate higher than that of most cancers. Myocardial disease in heart failure is frequently accompanied by impairment of the specialized electrical conduction system and myocardium. We introduce an epicardial mesh made of electrically conductive and mechanically elastic material, to resemble the innate cardiac tissue and confer cardiac conduction system function, to enable electromechanical cardioplasty. Our epicardium-like substrate mechanically integrated with the heart and acted as a structural element of cardiac chambers. The epicardial device was designed with elastic properties nearly identical to the epicardial tissue itself and was able to detect electrical signals reliably on the moving rat heart without impeding diastolic function 8 weeks after induced myocardial infarction. Synchronized electrical stimulation over the ventricles by the epicardial mesh with the high conductivity of 11,210 S/cm shortened total ventricular activation time, reduced inherent wall stress, and improved several measures of systolic function including increases of 51% in fractional shortening, ~90% in radial strain, and 42% in contractility. The epicardial mesh was also capable of delivering an electrical shock to terminate a ventricular tachyarrhythmia in rodents. Electromechanical cardioplasty using an epicardial mesh is a new pathway toward reconstruction of the cardiac tissue and its specialized functions.

Sizing by Weighing: Characterizing Sizes of Ultrasmall-Sized Iron Oxide Nanocrystals Using MALDI-TOF Mass Spectrometry

We present a rapid and reliable method for determining the sizes and size distributions of <5 nm-sized iron oxide nanocrystals (NCs) using matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry (MS). MS data were readily converted to size information using a simple equation. The size distribution obtained from the mass spectrum is well-matched with the data from transmission electron microscopy, which requires long and tedious analysis work. The size distribution obtained from the mass spectrum is highly resolved and can detect size differences of only a few angstroms. We used this MS-based technique to investigate the formation of iron oxide NCs, which is not easy to monitor with other methods. From ex situ measurements, we observed the transition from molecular precursors to clusters and then finally to NCs.

Stem-piped light activates phytochrome B to trigger light responses in Arabidopsis thaliana roots

Light conducted through plant tissues activates a photoreceptor in the roots of Arabidopsis thaliana. Plant stems pipe light to roots Light affects not only the development and physiology of the shoots (stems, leaves, and flowers) of plants but also the underground root system. Light triggers shoot cells to release signals that travel to the root and affect the development and physiology of the root system. Like shoot cells, root cells also have photoreceptors that can be activated by light, leading Lee et al. to investigate if light actually reaches these underground parts of the plant. Exposing Arabidopsis thaliana shoots to light while protecting the roots from light activated the photoreceptor phyB in the roots. In the root, phyB activated Hy5, a transcription factor that mediates cellular responses to light and was important for growth of the primary root and for root gravitropism, the proper downward orientation of roots. Arabidopsis stems efficiently conducted only certain wavelengths of light to the root tissues, and these conducted wavelengths activated phyB directly in the roots. These findings demonstrate that roots not only receive information about light conditions through signaling molecules that travel from the shoot to the root in response to light but also directly perceive light that is conducted through the plant tissues. The roles of photoreceptors and their associated signaling mechanisms have been extensively studied in plant photomorphogenesis with a major focus on the photoresponses of the shoot system. Accumulating evidence indicates that light also influences root growth and development through the light-induced release of signaling molecules that travel from the shoot to the root. We explored whether aboveground light directly influences the root system of Arabidopsis thaliana. Light was efficiently conducted through the stems to the roots, where photoactivated phytochrome B (phyB) triggered expression of ELONGATED HYPOCOTYL 5 (HY5) and accumulation of HY5 protein, a transcription factor that promotes root growth in response to light. Stimulation of HY5 in response to illumination of only the shoot was reduced when root tissues carried a loss-of-function mutation in PHYB, and HY5 mutant roots exhibited alterations in root growth and gravitropism in response to shoot illumination. These findings demonstrate that the underground roots directly sense stem-piped light to monitor the aboveground light environment during plant environmental adaptation.

Colloidal synthesis and thermoelectric properties of La-doped SrTiO3 nanoparticles

We describe n-type nanostructured bulk thermoelectric La-doped SrTiO3 materials produced by spark plasma sintering of chemically synthesized colloidal nanocrystals. The La doping levels could be readily controlled from 3 to 9.0 at% by varying the experimental conditions. We found that nanoscale interfaces were preserved even after the sintering process, and the thermoelectric properties of the nanostructured bulk La-doped SrTiO3 were characterized. An enhanced thermoelectric efficiency was observed and attributed to the large decrease in thermal conductivity obtained with no significant change in the Seebeck coefficient or electrical conductivity. The nanostructured bulk of the La-doped SrTiO3 exhibited a maximum ZT of ∼0.37 at 973 K at 9.0 at% La doping, which is one of the highest values reported for doped SrTiO3. Furthermore, the materials showed high thermal stability, which is important for practical high-temperature thermoelectric applications. This report demonstrates the high potential for low-cost thermoelectric energy production using highly stable and inexpensive oxide materials.