Seong Deok Kong

Magnetically vectored nanocapsules for tumor penetration and remotely switchable on-demand drug release

Nanocapsules containing intentionally trapped magnetic nanoparticles and defined anticancer drugs have been prepared to provide a powerful magnetic vector under moderate gradient magnetic fields. These nanocapsules can penetrate into the interior of tumors and allow a controlled on-off switchable release of the drug cargo via remote RF field. This smart drug delivery system is compact as all the components can be self-contained in 80-150 nm capsules. In vitro as well as in vivo results indicate that these nanocapsules can be enriched near the mouse breast tumor and are effective in reducing tumor cell growth.

Magnetic targeting of nanoparticles across the intact blood–brain barrier

Delivery of therapeutic or diagnostic agents across an intact blood-brain barrier (BBB) remains a major challenge. Here we demonstrate in a mouse model that magnetic nanoparticles (MNPs) can cross the normal BBB when subjected to an external magnetic field. Following a systemic administration, an applied external magnetic field mediates the ability of MNPs to permeate the BBB and accumulate in a perivascular zone of the brain parenchyma. Direct tracking and localization inside endothelial cells and in the perivascular extracellular matrix in vivo was established using fluorescent MNPs. These MNPs were inert and associated with low toxicity, using a non-invasive reporter for astrogliosis, biochemical and histological studies. Atomic force microscopy demonstrated that MNPs were internalized by endothelial cells, suggesting that trans-cellular trafficking may be a mechanism for the MNP crossing of the BBB observed. The silica-coated magnetic nanocapsules (SiMNCs) allow on-demand drug release via remote radio frequency (RF) magnetic field. Together, these results establish an effective strategy for regulating the biodistribution of MNPs in the brain through the application of an external magnetic field.

Magnetic field activated lipid-polymer hybrid nanoparticles for stimuli-responsive drug release.

Stimuli-responsive nanoparticles (SRNPs) offer the potential of enhancing the therapeutic efficacy and minimizing the side-effects of chemotherapeutics by controllably releasing the encapsulated drug at the target site. Currently controlled drug release through external activation remains a major challenge during the delivery of therapeutic agents. Here we report a lipid-polymer hybrid nanoparticle system containing magnetic beads for stimuli-responsive drug release using a remote radio frequency (RF) magnetic field. These hybrid nanoparticles show long-term stability in terms of particle size and polydispersity index in phosphate-buffered saline (PBS). Controllable loading of camptothecin (CPT) and Fe(3)O(4) in the hybrid nanoparticles was demonstrated. RF-controlled drug release from these nanoparticles was observed. In addition, cellular uptake of the SRNPs into MT2 mouse breast cancer cells was examined. Using CPT as a model anticancer drug the nanoparticles showed a significant reduction in MT2 mouse breast cancer cell growth in vitro in the presence of a remote RF field. The ease of preparation, stability, and controllable drug release are the strengths of the platform and provide the opportunity to improve cancer chemotherapy.

Antibiofouling, sustained antibiotic release by Si nanowire templates.

Loading or filling nanostructures with antibiotics can be one of the relevant approaches for obtaining a controlled drug release rate. Vertically aligned silicon nanowire (SiNW) arrays with 10-40 nm diameter wires having 1-3 microm in length obtained by the electroless etching (EE) technique are used in this study as novel nanostructures for mediating drug delivery. Here we report controlled antibiotic activity and sustained bioavailability from SiNW arrays and also show microstructural manipulations for a tunable release rate. As well, we have demonstrated biodegradability of SiNWs in phosphate buffer saline (PBS) solution. Strikingly suppressed cell and protein adhesion was observed on our SiNW surface, which indicates a reduced probability for biofouling and drug release impediments. Such antibiotic release from the nanowire-structured surface can provide more reliable antibiotic protection at a targeted implantation or biosensor site.

Preparation of near micrometer-sized TiO2 nanotube arrays by high voltage anodization.

Highly ordered TiO2 nanotube arrays with large diameter of 680-750 nm have been prepared by high voltage anodization in an electrolyte containing ethylene glycol at room temperature. To effectively suppress dielectric breakdown due to high voltage, pre-anodized TiO2 film was formed prior to the main anodizing process. Vertically aligned, large sized TiO2 nanotubes with double-wall structure have been demonstrated by SEM in detail under various anodizing voltages up to 225 V. The interface between the inner and outer walls in the double-wall configuration is porous. Surface topography of the large diameter TiO2 nanotube array is substantially improved and effective control of the growth of large diameter TiO2 nanotube array is achieved. Interestingly, the hemispherical barrier layer located at the bottom of TiO2 nanotubes formed in this work has crinkles analogous to the morphology of the brain cortex. These structures are potentially useful for orthopedic implants, storage of biological agents for controlled release, and solar cell applications.

In vivo nanoneurotoxicity screening using oxidative stress and neuroinflammation paradigms

UNLABELLED Iron oxide nanoparticles (IONPs) are promising neuroimaging agents and molecular cargo across neurovascular barriers. Development of intrinsically safe IONP chemistries requires a robust in vivo nanoneurotoxicity screening model. Herein, we engineered four IONPs of different surface and core chemistries: DMSA-Fe2O3, DMSA-Fe3O4, PEG-Fe3O4 and PEG-Au-Fe3O4. Capitalizing on the ability of the peripheral nervous system to recruit potent immune cells from circulation, we characterized a spatiotemporally controlled platform for the study of in vivo nanobiointerfaces with hematogenous immune cells, neuroglial and neurovascular units after intraneural IONP delivery into rat sciatic nerve. SQUID magnetometry and histological iron stain were used for IONP tracking. Among the IONPs, DMSA-Fe2O3 NPs were potent pro-apoptotic agents in nerve, with differential ability to regulate oxidative stress, inflammation and apoptotic signaling in neuroglia, macrophages, lymphocytes and endothelial cells. This platform aims to facilitate the development of predictive paradigms of nanoneurotoxicity based on mechanistic investigation of relevant in vivo bio-nanointerfaces. FROM THE CLINICAL EDITOR This team of investigators report the development of a platform that enables screening of iron oxide nanoparticles from the standpoint of their potential neurotoxicity, utilizing rat sciatic nerves. Such screening tools are clearly needed with the potential advent of iron oxide nanoparticle-based diagnostic and therapeutic approaches.

Magnetically guided nano-micro shaping and slicing of silicon.

Silicon is one of the most important materials for modern electronics, telecom, and photovoltaic (PV) solar cells. With the rapidly expanding use of Si in the global economy, it would be highly desirable to reduce the overall use of Si material, especially to make the PVs more affordable and widely used as a renewable energy source. Here we report the first successful direction-guided, nano/microshaping of silicon, the intended direction of which is dictated by an applied magnetic field. Micrometer thin, massively parallel silicon sheets, very tall Si microneedles, zigzag bent Si nanowires, and tunnel drilling into Si substrates have all been demonstrated. The technique, utilizing narrow array of Au/Fe/Au trilayer etch lines, is particularly effective in producing only micrometer-thick Si sheets by rapid and inexpensive means with only 5 μm level slicing loss of Si material, thus practically eliminating the waste (and also the use) of Si material compared to the ~200 μm kerf loss per slicing and ~200 μm thick wafer in the typical saw-cut Si solar cell preparation. We expect that such nano/microshaping will enable a whole new family of novel Si geometries and exciting applications, including flexible Si circuits and highly antireflective zigzag nanowire coatings.

An X–Y Addressable Matrix Odor‐Releasing System Using an On–Off Switchable Device

In recent decades, much research has been dedicated to the development of virtual reality for entertainment, engineering, and medical application. Virtual reality can be made more realistic with an artificial three-dimensional visual or other sensory environment using the experience of moving seats, odors of explosives or flowers, sprinkling water, laser lights, and wind blowing. Odor-releasing devices that allow repeatable, remote, and reliable switching of odor flux, in particular, could have a significant impact on the effectiveness of virtual reality. However, although various devices for the added sense experience have been developed recently, very few odor-generating devices with practical and useful control of induced sense of smell have been reported. The development of an odor-releasing system that can provide specific odor selectively began in the early days as a crude device. The oldest system is “Sensorama”, a game machine, wherein odor is presented according to the scene on the display and the chair or steering wheel vibrates. After Sensorama, there were discussions about which movie needs odor presentation, referring to some experiments on providing odors synchronously as the movie scenes evolve. In the AMLUX theatre, there was an attempt to add odor information to visual media. Also, there have been some tests to induce the relaxation effect through odor presentation in art objects. Furthermore, there were some approaches to utilize odor information for the fire-fighter training system, and the soldier training system by using a scent collar. These systems present odor information by evaporating bulk smelly material or by spraying it using propellant gas or inkjet technology. However, these well-known technologies are coarse and crude in nature, and it is hard to apply them to delicate home electronics or personal devices owing to their bulkiness, their lack of reproducible release over multiple cycles, their slow response times to stimuli, as well as their inability to dynamically adjust the amount/intensity of odor according to the recipient s needs. Therefore, the development of odorreleasing or transferring systems for the electronic device virtual reality has been difficult. Moreover, televisions, hometheatre, or video-game devices are getting thinner and smaller, requiring faster and more accurate control. Indeed, no existing device could overcome all of these limitations at the moment. For example, an automatic aerosol dispenser containing odor-filled reservoirs can achieve rapid on-demand odor delivery but the odor-storing cans are filled with compressed gas or flammable solvents used as propellants and require a complicated valve system which is difficult to scale down. The desirable odor-generating systems should not depend on a mechanical switching system and should be thin enough to insert into small devices. For these reasons, innovative technologies are needed. The primary requirement to the development of a gas-release device for odor generation is an accurate control capability. From this perspective, an ideal device for odor generation should safely contain a suitable quantity of odor-releasable solution, can release little or no odor in the “off” state, and be repeatedly switched to the “on” state without mechanically disrupting the device. In recent years, many researchers have been trying to develop on–off switchable devices for drug release using polymers, because some polymers have good reversible switching properties. We have employed in our new odorgenerating system, a stable polymer, polydimethylsiloxane (PDMS), a representative silicone elastomer. PDMS is optically clear and, in general, is considered to be inert, non-toxic, and non-flammable. One of the primary fields of applications for PDMS is the embedding or encapsulation of electronic components by casting, which prolongs the lifespan of the circuit chips. A silicone elastomer such as PDMS, exhibits mechanical elasticity, acts as a dielectric isolator, and protects the components from environmental factors and mechanical shock over a relatively large temperature span (e.g., 50–200 8C). In addition, the inertness and stability of PDMS has been traditionally utilized as a biomaterial in implants, catheters, drainage tubing, and membrane oxygenators. We have therefore utilized the desirable properties of PDMS for the development of our on–off switchable odor releasing system. Cross-linked (cured) PDMS elastomer does not allow aqueous solvents to infiltrate and swell the polymer, so that it can be used as a container which can store a water-based liquid. Although elastomers are not [*] H. Kim, K. Noh, C. J. Gardner, Dr. S. D. Kong, Prof. Dr. S. Jin Materials Science and Engineering University of California, San Diego 9500 Gilman Drive, La Jolla, CA 92093-0411 (USA) Fax: (+ 1)858-534-5698 E-mail: jin@ucsd.edu Homepage: http://maeweb.ucsd.edu/~ jin/ Dr. J. Park, Dr. J. Kim Samsung Advanced Institute of Technology, Frontier Research Lab Samsung Electronics Co., Ltd. Suwon, Gyeonggi-Do 443-742 (Korea) Fax: (+ 82)31-280-9349 E-mail: jongkim@samsung.com [] These authors contributed equally.

Nanocomposites of TiO2 and double-walled carbon nanotubes for improved dye-sensitized solar cells

It is demonstrated that an incorporation of double-walled carbon nanotubes (DWCNTs) into a TiO2 photo-anode layer results in a significant improvement in the overall energy conversion performance in the dye-sensitized solar cell (DSSC). Comparing to the standard TiO2 anode, the carbon nanotube-containing TiO2 anode with 0.2 wt. % DWCNTs has boosted up the photocurrent density (Jsc) by 43%. The DSSC power conversion efficiency was also improved from ∼3.9% in the case of carbon nanotube-free TiO2 anode to as high as 6.4% with the addition of DWCNTs upon optimized anode annealing. The observed enhancement in the solar cell performance in the presence of the carbon nanotubes is attributed primarily to the noticeable reduction in microcracking and associated robust electrical conduction. Some contribution of the electrical conducting nature of the filler material (DWCNTs) to the improved DSSC properties may be possible; however, it is viewed as a minor effect, considering the small amount of the nanotubes used.

Magnetically Vectored Delivery of Cancer Drug Using Remotely On–Off Switchable NanoCapsules

Hollow-sphere-structured magnetic nanocapsules containing intentionally trapped iron oxide nanoparticles and anticancer drugs have been prepared to provide a powerful magnetic vector under moderate gradient magnetic fields. It is shown that these nanocapsules can penetrate into the interior of tumors and allow a controlled on-off switchable release of the anticancer drug cargo via remote 100 KHz RF field. This smart drug delivery system is nanoscale compact, with the drug molecules and magnetic nanoparticles contained within the hollow capsules having ~ 80 ~ 150nm diameter. In vitro results using a mouse model indicate that such a nanocapsule-mediated, on-demand drug release is effective in reducing tumor cell growth.