Taeksu Lee

Efficient CD44-targeted magnetic resonance imaging (MRI) of breast cancer cells using hyaluronic acid (HA)-modified MnFe2O4 nanocrystals.

Targeted molecular imaging with hyaluronic acid (HA) has been highlighted in the diagnosis and treatment of CD44-overexpressing cancer. CD44, a receptor for HA, is closely related to the growth of cancer including proliferation, metastasis, invasion, and angiogenesis. For the efficient detection of CD44, we fabricated a few kinds of HA-modified MnFe2O4 nanocrystals (MNCs) to serve as specific magnetic resonance (MR) contrast agents (HA-MRCAs) and compared physicochemical properties, biocompatibility, and the CD44 targeting efficiency. Hydrophobic MNCs were efficiently phase-transferred using aminated polysorbate 80 (P80) synthesized by introducing spermine molecules on the hydroxyl groups of P80. Subsequently, a few kinds of HA-MRCAs were fabricated, conjugating different ratios of HA on the equal amount of phase-transferred MNCs. The optimized conjugation ratio of HA against magnetic content was identified to exhibit not only effective CD44 finding ability but also high cell viability through in vitro experiments. The results of this study demonstrate that the suggested HA-MRCA shows strong potential to be used for accurate tumor diagnosis.

Gadolinium‐Enriched Polyaniline Particles (GPAPs) for Simultaneous Diagnostic Imaging and Localized Photothermal Therapy of Epithelial Cancer

By loading Gd(III) inside NIR-absorbing polyaniline nanostructures, a novel diagnostic and photothermal agent with enhanced MR sensitivity, targeting ability, and photothermal ability to treat epithelial cancer is developed.

Self-fabricated dextran-coated gold nanoparticles using pyrenyl dextran as a reducible stabilizer and their application as CT imaging agents for atherosclerosis

A facile method to produce dextran-coated gold nanoparticles (DGNPs) for atherosclerosis detection using computed tomography (CT) imaging is developed. DGNPs are prepared using only pyrenyl dextran as a reducible stabilizer chemically conjugated with hydroxyl groups of dextran and carboxyl groups of pyrenyl molecules, which can reduce gold ions to gold particles and stably form gold nanoparticles in the aqueous phase. The physical properties of DGNPs can be controlled by the reaction time. DGNPs, where gold particles were stably covered with dextran, exhibit targeting ability against inflammatory macrophages with the help of strong interactions between dextran on their surface and scavenger receptors in the macrophages with good biocompatibility without cell damage. From the in vivo studies, DGNPs can be used to accurately detect atherosclerosis via CT imaging.

One-step electrochemical fabrication of vertically self-organized silver nanograss

Fabrication of one dimensional metal nanomaterials offers many beneficial aspects due to their unique size- and shape-dependent characteristics. However, facile fabrication of a robust one dimensional nanostructure has still remained a great challenge. Here, we developed a new synthetic route of one-step electrochemical deposition of silver nanograss without the assistance of a template. By applying an overpotential of −2.0 V (vs. Ag/AgCl) under aqueous alkaline conditions, silver nanograss with a slight tilt in a randomly oriented direction was spontaneously formed on the working electrode surface. Two applications that utilize advantageous features of this silver nanograss were demonstrated: (i) an efficient surface-enhanced Raman scattering substrate for a chemical sensor and (ii) an enzyme-less hydrogen peroxide sensor. Compared to silver nanowire arrays fabricated using anodized aluminum oxide (AAO) templates, the silver nanograss exhibited comparable hydrogen sensing due to its catalytic hydrogen peroxide reduction activity and produced a much stronger surface-enhanced Raman spectroscopy (SERS) signal due to its innate structure.

Comparative hyperthermia effects of silica-gold nanoshells with different surface coverage of gold clusters on epithelial tumor cells.

Silica–gold nanoshell (SGNS), which is a silica core surrounded by a gold layer, was synthesized by seed-mediated coalescence of gold clusters in an electroless plating solution. SGNS variations with different surface coverage of gold clusters were prepared by adjusting the amounts of gold salts in the presence of formaldehyde-reducing agents. Fully covered SGNS (f-SGNS) with connected gold clusters exhibited stronger intensity and more redshift of plasmon bands located around 820 nm than those of partially covered SGNS (p-SGNS) with disconnected gold clusters. Upon irradiation with near-infrared light (30 W/cm2, 700–800 nm), f-SGNS caused a larger hyperthermia effect, generating a large temperature change (ΔT =42°C), as compared to the relatively small temperature change (ΔT =24°C) caused by p-SGNS. The therapeutic antibody, Erbitux™ (ERB), was further conjugated to SGNS for specific tumor cell targeting. The f-ERB-SGNS showed excellent therapeutic efficacy based on the combined effect of both the therapeutic antibody and the full hyperthermia dose under near-infrared irradiation. Thus, SGNS with well-controlled surface morphology of gold shells may be applicable for near-infrared-induced hyperthermia therapy with tunable optical properties.

A multistep photothermic-driven drug release system using wire-framed Au nanobundles.

Here, wire-framed Au nanobundles (WNBs), which consist of randomly oriented and mutually connected Au wires to form a bundle shape, are synthesized. In contrast to conventional nanoparticles (spheres, rods, cubes, and stars), which exhibit nanostructure only on the surface, cross-sectional view image shows that WNBs have nanostructures in a whole volume. By using this specific property of WNBs, an externally controllable multistep photothermic-driven drug release (PDR) system is demonstrated for in vivo cancer treatment. In contrast to conventional nanoparticles that encapsulate a drug on their surface, WNBs preserve the drug payload in the overall inner volume, providing a drug loading capacity sufficient for cancer therapy. An improved in vivo therapeutic efficacy of PDR therapy is also demonstrated by delivering sufficient amount of drugs to the target tumor region.

Cancer theranosis using mono-disperse, mesoporous gold nanoparticles obtained via a robust, high-yield synthetic methodology

Porous noble metal nanoparticles exhibit many attractive nanoplasmonic features, and these structures have potential applications in many fields. However, such applications have been hindered by a lack of synthetic methods with the ability to mass-produce mono-disperse nanoparticles. Current synthetic approaches to porous gold nanostructure fabrication involve galvanic replacement approaches or electrochemical deposition methods that are generally limited by stringent multi-step protocols and relatively low yields. Here, we introduce the facile synthesis of scalable, mono-disperse, mesoporous gold nanoparticles (MPGNs) using an acidic emulsification method. This method facilitates high synthetic yields (>93%) and tunable particle sizes (130–400 nm). MPGNs exhibit enhanced payloads of gadolinium (Gd), a contrast agent for magnetic resonance imaging. Additionally, they permit photo-thermal conversion under near-infrared light (NIR) irradiation due to the increased surface area to volume ratio and the unique, structure-mediated LSPR effect. Specifically, MPGNs fabricated using our method provided Gd payloads 2–4 orders of magnitude greater than previously reported theranostic nano-probes. We believe that our novel synthetic technique will not only contribute to large-scale production of homogeneous porous gold nanoparticles, but will also promote further research in porous noble metal nanostructures.

One-pot synthesis of magnetic nanoclusters enabling atherosclerosis-targeted magnetic resonance imaging

In this study, dextran-encrusted magnetic nanoclusters (DMNCs) were synthesized using a one-pot solution phase method for detection of atherosclerosis by magnetic resonance imaging. Pyrenyl dextran was used as a surfactant because of its electron-stabilizing effect and its amphiphilic nature, rendering the DMNCs stable and water-dispersible. The DMNCs were 65.6±4.3 nm, had a narrow size distribution, and were superparamagnetic with a high magnetization value of 60.1 emu/g. Further, they showed biocompatibility and high cellular uptake efficiency, as indicated by a strong interaction between dextran and macrophages. In vivo magnetic resonance imaging demonstrated the ability of DMNCs to act as an efficient magnetic resonance imaging contrast agent capable of targeted detection of atherosclerosis. In view of these findings, it is concluded that DMNCs can be used as magnetic resonance imaging contrast agents to detect inflammatory disease.

Minimum hyaluronic acid (HA) modified magnetic nanocrystals with less facilitated cancer migration and drug resistance for targeting CD44 abundant cancer cells by MR imaging

We report minimal amount of hyaluronic acid (HA) conjugated magnetic nanocrystals (mHMs) for targeted imaging of CD44 abundant breast cancer cells via MRI. These mHMs lead to less induced cancer migration and drug resistance, which is distinct from conventional approaches using nanoplatforms (imaging or therapeutic systems) that are completely covered with HA. To synthesize mHMs, magnetic nanocrystals (MNCs), as MRI contrast agents, were encapsulated mostly with polysorbate 80 (P80, non-reactive to HA) and partially with aminated P80 (reactive to HA). This system enabled conjugation of an immensely diminished amount of HA onto MNCs. While these nanoparticles maintained good CD44 targeted imaging efficacy, they also showed no cytotoxicity and colloidal stability. We varied the HA ratios on an equal amount of MNCs and identified that when more HA was attached on nanoparticles, there was more facilitated cancer migration and drug resistant potentials. We chose the lowest amount of HA conjugated mHMs (mHM1) and demonstrated that mHM1 selectively diagnosed tumor regions in vivo. We believe that the technique described herein can be applied to various applications using HA to detect CD44 abundant cancer cell lines and offer a basis to understand the interaction between the cellular response and surface modification of nanoparticles.

Optimal DNA structure of reverse-hairpin beacons for label-free and positive surface enhanced Raman scattering assays

We developed a label-free and positive-readout surface enhanced Raman scattering (SERS) assay using reverse-hairpin molecular beacons (RHBs) for the detection of RNA genetic markers associated with a high pathogenicity influenza (HPAI) virus. The structure of RHBs flexibly changed from a linear configuration (open state) to hairpin (closed state) upon targeting, such that the Raman label was closed on the SERS substrate and induced an increase of SERS intensity (OFF-to-ON). By improving sequence-specific RNA/DNA hybridization efficiency, we adjusted the stem-loop ratio of RHB, which was efficient at values of less than 1. The optimized RHBs exhibited dramatic changes in signal based on a fluorescence system in which the target was present. We demonstrated that the OFF-to-ON SERS system using RHB immobilized on silver-coated gold nanobowls permitted rapid hybridization. This proof-of-concept could provide a potential diagnostic tool for point-of-care influenza virus detection.