Giyoong Tae

Enzyme-mediated generation of reactive oxygen species (ROS) has attracted considerable interest for cancer-related applications. However, the biomedical use of oxidase enzymes is often limited by their intrinsic instability and rapid...

Conventional tumor-targeted therapies primarily focus on drug delivery systems exploiting the tumor microenvironment for controlled drug release. While prodrug strategies activate small-molecule drugs in tumors, they rely on single-step chemical conversions and lack sustained tumor-selective activity. Here, a novel strategy of tumor-responsive, enzymatic cascade therapy is introduced by co-delivering arginine decarboxylase (RDC) and diamine oxidase (DAO) into the tumor site. Unlike traditional arginine depletion strategies, RDC remains inactive at physiological pH and is selectively activated under acidic tumor conditions, ensuring localized metabolic starvation while minimizing systemic toxicity. To overcome a key limitation of RDC—namely, the accumulation of toxic agmatine—RDC is co-delivered with DAO using a chitosan-functionalized Pluronic-based nanocarrier (RDC/DAO@NC), enabling tumor-specific conversion of agmatine into hydrogen peroxide (H ₂ O ₂ ). This pH-sensitive cascade reaction is expected to limit agmatine accumulation in normal tissues while amplifying RDC-mediated antitumor effects through oxidative-stress-induced apoptosis. In vitro, RDC/DAO@NC suppresses tumor cell proliferation through arginine depletion and induces apoptosis via H ₂ O ₂ generation. In vivo, RDC/DAO@NC substantially enhances tumor accumulation and therapeutic efficacy compared to free enzymes. This study provides the first in vivo validation of RDC-based cancer therapy, suggesting its potential as a tumor-selective strategy integrating enzyme activation in the tumor microenvironment, metabolic starvation, and reactive-oxygen-species-induced apoptosis in cancer treatment.

Kidney disease has emerged as a significant public health concern, affecting approximately 10 % of adults worldwide. Especially, acute kidney injury (AKI) increases in-hospital morbidity and mortality. This study introduces a dual-therapeutic strategy combining interleukin-10 (IL-10), an anti-inflammatory cytokine, and catalase (CAT), a reactive oxygen species (ROS)-scavenging enzyme, for the treatment of inflammatory kidney injury. A kidney-targeting peptide-conjugated, Pluronic-based nanocarrier (K-NC) was developed to enable the co-delivery and sustained release of IL-10 and CAT. Compared to no-ligand conjugated NC, K-NC was selectively accumulated in the damaged kidneys while reducing liver accumulation. In vitro, CAT effectively reduced ROS levels in tubular epithelial cells, while IL-10 suppressed inflammatory cytokine expression and promoted M2 macrophage polarization. In vivo, co-delivery of IL-10 and CAT using K-NC resulted in significantly enhanced therapeutic effects on AKI compared to single delivery of IL-10 or CAT using K-NC (IL-10@K-NC or CAT@K-NC), or co-delivery of IL-10 and CAT using no-ligand conjugated NC (IL-10/CAT@NC) by showing reduced levels of serum creatinine and BUN, reduced reactive oxygen species, reduced pro-inflammatory cytokine expression, inhibited M1 macrophage polarization, and promoted M2 macrophage polarization in the kidney. This study not only presents a promising approach for the treatment of kidney inflammation but is also the first report demonstrating enhanced therapeutic effects through a combination of an antioxidant enzyme with an anti-inflammatory cytokine.

Over the past few decades, extensive research has explored the development of supportive scaffold materials for in vitro hepatic cell culture, to effectively mimic in vivo microenvironments. It is crucial for hepatic disease modeling, drug screening, and therapeutic evaluations, considering the ethical concerns and practical challenges associated with in vivo experiments. This review offers a comprehensive perspective on hepatic cell culture using bioscaffolds by encompassing all stages of hepatic diseases—from a healthy liver to fibrosis and hepatocellular carcinoma (HCC)—with a specific focus on matrix stiffness. This review begins by providing physiological and functional overviews of the liver. Subsequently, it explores hepatic cellular behaviors dependent on matrix stiffness from previous reports. For hepatic cell activities, softer matrices showed significant advantages over stiffer ones in terms of cell proliferation, migration, and hepatic functions. Conversely, stiffer matrices induced myofibroblastic activation of hepatic stellate cells, contributing to the further progression of fibrosis. Elevated matrix stiffness also correlates with HCC by increasing proliferation, epithelial-mesenchymal transition, metastasis, and drug resistance of HCC cells. In addition, we provide quantitative information on available data to offer valuable perspectives for refining the preparation and development of matrices for hepatic tissue engineering. We also suggest directions for further research on this topic.

This research presents a simple but general method to prepare water-soluble-polymer-based superabsorbent hydrogels with predefined microscale geometries and controlled swelling properties. Unlike conventional hydrogel preparation methods based on bulk solution-phase cross-linking, poly(vinyl alcohol) is homogeneously mixed with polymer-based cross-linkers in the solution phase and thermally cross-linked in the solid phase after drying; the degree of cross-linking is modulated by controlling the cross-linker concentration, pH, and/or thermal annealing conditions. After the shape definition process, cross-linked films or electrospun nanofibers are treated with sulfuric acid to weaken hydrogen bonds and introduce sulfate functionality in polymer crystallites. The resultant superabsorbent hydrogels exhibit an isotropic expansion of the predefined geometry and tunable swelling properties. Particularly, hydrogel microfibers exhibit excellent optical transparency, good biocompatibility, large porosity, and controlled cell adhesion, leading to versatile 3D cell culture scaffolds that not only support immortalized cell lines and primary neurons but also enable stiffness-modulated cell adhesion studies.

Heparinized PEEK via a green method provided a sustained release of loaded BMP-2, leading to enhanced osteogenic activity of an osteoblast cell line. This strategy could improve the osseointegration of PEEK-based bone implants.