Yoochan Hong

Nanobiosensors based on localized surface plasmon resonance for biomarker detection

Localized surface plasmon resonance (LSPR) is induced by incident light when it interacts with noblemetal nanoparticles that have smaller sizes than the wavelength of the incident light. Recently, LSPR-based nanobiosensors were developed as tools for highly sensitive, label-free, and flexible sensing techniques for the detection of biomolecular interactions. In this paper, we describe the basic principles of LSPR-based nanobiosensing techniques and LSPR sensor system for biomolecule sensing. We also discuss the challenges using LSPR nanobiosensors for detection of biomolecules as a biomarker.

Highly selective CD44-specific gold nanorods for photothermal ablation of tumorigenic subpopulations generated in MCF7 mammospheres

Heterogeneous stem-like populations within tumor tissues are the primary suspects in causing cancer recurrence and malignancy. It is essential to selectively kill these tumorigenic populations. We created a novel system for photothermally ablating specific cells from three-dimensional mammospheres. A CD44-positive subpopulation, with tumorigenic and self-renewal potential, spontaneously arises in MCF7 breast cancer cell-engineered mammospheres. Using anti-CD44 antibody-linked gold nanorods, which strongly absorb near infrared light and increase local temperature, we effectively targeted and photo-ablated atypical cells. This biomarker-specific photothermal ablation model, using a smart nanoplatform, is a promising new strategy for selectively killing cancer cells, while sparing normal tissues.

Aptamer-conjugated gold nanorod for photothermal ablation of epidermal growth factor receptor-overexpressed epithelial cancer.

Abstract. Biomarker-specific photothermal nanoparticles that can efficiently sense markers that are overexpressed in distinguished adenocarcinomas have attracted much interest in an aspect of efficacy increase of cancer treatment. We demonstrated a promising prospect of a smart photothermal therapy agent employing anti-epidermal growth factor receptor aptamer (AptEGFR)-conjugated polyethylene glycol (PEG) layted gold nanorods (AptEGFR-PGNRs). The cetyltrimethylammonium bromide bilayer on GNRs was replaced with heterobifunctional PEG (COOH-PEG-SH) not only to serve as a biocompatible stabilizer and but also to conjugate AptEGFR. Subsequently, to direct photothermal therapy agent toward epithelial cancer cells, the carboxylated PEGylated GNRs (PGNRs) were further functionalized with AptEGFR using carbodiimide chemistry. Then, to assess the potential as biomarker-specific photothermal therapy agent of synthesized AptEGFR-PGNRs, the optical properties, biocompatibility, colloidal stability, binding affinity, and epicellial cancer cell killing efficacy in vitro/in vivo under near-infrared laser irradiation were investigated. As a result, AptEGFR-PGNRs exhibit excellent tumor targeting ability and feasibility of effective photothermal ablation cancer therapy.

The efficacy of portal vein embolization prior to right extended hemihepatectomy for hilar cholangiocellular carcinoma: A retrospective cohort study

BACKGROUND/PURPOSE Preoperative portal vein embolization was introduced to minimize complications after extended hepatectomy. This retrospective cohort study was conducted to compare outcomes with and without portal vein embolization before hepatectomy for hilar cholangiocellular carcinoma. METHODS This study was conducted with 35 patients who underwent right extended hemihepatectomy for hilar cholangiocellular carcinoma from 2001 to 2008. Preoperative portal vein embolization was performed in 14 patients (embolization group) and not performed in 21 patients (non-embolization group). RESULTS The groups did not differ in terms of sex, age, operative time, transfusion, postoperative serum bilirubin level, prothrombin time, and length of intensive care unit (ICU) stay. Although blood loss was higher in the embolization group than in the non-embolization group (P = .009), no major complications were observed between embolization and resection. At presentation, future liver remnant was smaller in the embolization group (19.8%, range 16-35%) than in non-embolization group (28.3%, 15-47%; P = .001). After embolization, the volume of the future liver remnant increased significantly to 27.2% (range, 23-42%; P = .001). Future liver remnants just before operation were similar in both groups (P > .99). There was no significant difference in terms of the rate of morbidity and in-hospital mortality. No statistically significant differences were observed in disease-free survival (P = .52) and overall survival (P = .30). CONCLUSIONS Portal vein embolizations do not increase the rate of morbidity, in-hospital mortality, local recurrence and system metastasis. Therefore it can be considered safe and effective for patients with small future liver remnants. Embolization can lessen postoperative liver failure and widen the indication of the surgical resection, especially in patients with marginal future liver remnants.

Localized surface plasmon resonance based nanobiosensor for biomarker detection of invasive cancer cells

Abstract. In this study, we describe the development of a cancer biomarker-sensitive nanobiosensor based on localized surface plasmon resonance that enables recognition for proteolytic activity of membrane type 1 matrix metalloproteinase (MT1-MMP) anchored on invasive cancer cells. First of all, we prepared biomarker-detectable substrate based on gold nanorods (GNRs) using nanoparticle adsorption method. The sensitivity of the sensing chip was confirmed using various solvents that have different refractive indexes. Subsequently, MT1-MMP–specific cleavable peptide was conjugated onto the surface of GNRs, and molecular sensing about proteolytic activity was conducted using MT1-MMP and cell lysates. Collectively, we developed a biomarker detectable sensor, which allows for the effective detection of proteolytic activity about MT1-MMP extracted from invasive cancer cells.

CD44-specific supramolecular hydrogels for fluorescence molecular imaging of stem-like gastric cancer cells

We describe a near-infrared-sensitive molecular imaging probe based on hydrogel complexes that can target a stem-like gastric cancer cell marker (CD44, a marker that often correlates with a poor prognosis in patients). Thus, CD44-targetable and near-infrared-sensitive supramolecular hydrogels (NIRSHs, Cy5.5-conjugated polyethyleneimine/hyaluronic acid polyplexes) were fabricated by polyplexing in an aqueous medium. NIRSHs demonstrated good water-stability, biocompatibility, and specificity to CD44-expressing stem-like gastric cancer cells. Furthermore, NIR-sensitive in vivo imaging potentials of CD44-targetable NIRSHs for heterotopic/orthotopic xenograft mouse models were investigated.

In vivo sensing of proteolytic activity with an NSET-based NIR fluorogenic nanosensor.

Biomedical in vivo sensing methods in the near-infrared (NIR) range, which that provide relatively high photon transparency, separation from auto-fluorescence background, and extended sensitivity, are being used increasingly for non-invasive mapping and monitoring of molecular events in cancer cells. In this study, we fabricated an NIR fluorogenic nanosensor based on the nanoparticle surface energy transfer effect, by conjugation of fluorescent proteolytic enzyme-specific cleavable peptides with gold nanorods (GNRs). Membrane-anchored membrane type 1-matrix metalloproteinases (MT1-MMPs), a family of zinc-dependent proteolytic enzymes, can induce the metastatic potential of cancer cells by promoting degradation of the extracellular matrix. Therefore, sensitive detection of MT1-MMP activity can provide essential information in the clinical setting. We have applied in vivo NIR sensing to evaluate MT1-MMP activity, as an NIR imaging target, in an MT1-MMP-expressing metastatic tumor mouse model.

Redox-sensitive colorimetric polyaniline nanoprobes synthesized by a solvent-shift process

AbstractWe have synthesized water-stable polyaniline nanoparticles coated with triarmed polyethylene glycol chains using a solvent-shift method and confirmed their colloidal size and aqueous solubility. Furthermore, we have demonstrated that the polyaniline nanoparticles can be doped with biological dopants to produce distinct color changes allowing the detection of live cancer cells.

Gold nanorod-mediated photothermal modulation for localized ablation of cancer cells

We estimated the photothermal transduction efficiency of gold nanorod (GNR) solutions for different GNR concentrations and irradiation laser power. In particular, we verified that the degree of cell death area could be modulated by GNR concentration and irradiation laser power. The efficacy of GNR-produced photothermal ablation of cancer cells was evaluated by irradiating GNRs in the presence of MDA-MB-231 breast cancer cells with a near-infrared (NIR) laser at different laser power densities and irradiation times. GNR-induced photothermal ablation was applied successfully to cancer cells at various NIR laser power densities and irradiation times and was characterized with live-dead cell staining. Through these techniques, we established the system for not only verification of induced photothermal effect using NIR laser and thermocouple, but also identification of uptake efficiency for GNRs and cell viability using dark field and fluorescence imaging, respectively.

Photothermal ablation of cancer cells using self-doped polyaniline nanoparticles.

Water-stable confined self-doping polyaniline nanocomplexes are successfully fabricated by nano-assembly using lauric acid both as a stabilizer and as a localized dopant. In particular, the colloidal stability of the polyaniline nanocomplexes in neutral pH and the photothermal potential by near-infrared light irradiation are characterized. We demonstrate that confined self-doping polyaniline nanocomplexes as a photothermal nanoagent are preserved in the doped state even at a neutral pH. Finally, confined self-doping polyaniline nanocomplexes aided by lauric acid are successfully applied for the photothermal ablation of cancer cells.