Ja-Hyoung Ryu

Ulsan National Institute of Science and Technology | UNIST · Department of Chemistry

Intracellular assemblies play vital roles in maintaining cellular functions through structural recognition-mediated interactions. The introduction of artificial structures has garnered substantial interest in modulating cellular functions via activation/inhibition interactions with biomacromolecules. However, the cellular uptake of these high-molec...

Nanomedicine, which merges the realms of nanotechnology and medicine, presents transformative strategies for advancing healthcare through nanoscale manipulation of materials. Among these, metal–organic frameworks (MOFs), with a unique hybrid structure...

Chemotherapy using a nanoscaled drug delivery system is an effective cancer therapy, but its high drug concentration often causes drug resistance in cancer cells and normal cell damage. Combination therapy involving two or more different cell signaling pathways can be a powerful tool to overcome the limitations of chemotherapy. Herein, this article...

Advanced energy storage devices are indispensable for expanding electric mobility applications. While anion intercalation‐type redox chemistry in graphite cathodes has opened the path to high‐energy‐density batteries, surpassing the limited energy density of conventional lithium‐ion batteries (LIBs), a significant challenge remains: the large volum...

Senolytics, which eliminate senescent cells from tissues, represent an emerging therapeutic strategy for various age-related diseases. Most senolytics target antiapoptotic proteins, which are overexpressed in senescent cells, limiting specificity and inducing severe side effects. To overcome these limitations, we constructed self-assembling senolyt...

Lysosomes remain powerful organelles and important targets for cancer therapy because cancer cell proliferation is greatly dependent on effective lysosomal function. Recent studies have shown that lysosomal membrane permeabilization induces cell death and is an effective way to treat cancer by bypassing the classical caspase-dependent apoptotic pat...

Targeted delivery along with controlled drug release is considered crucial in development of a drug delivery system (DDS) for efficient cancer treatment. In this paper, we present a strategy to obtain such a DDS by utilizing disulfide-incorporated mesoporous organosilica nanoparticles (MONs), which were engineered to minimize the surface interactio...

Metal‐organic framework (MOF) nanoparticles have recently emerged as a promising vehicle for drug delivery with high porosity and feasibility. However, employing a MOF‐based drug delivery system remains a challenge due to the difficulty in controlling interfaces of particles in a biological environment. In this paper, protein corona‐blocked Zr6‐bas...

To achieve spatiotemporal control, an enzyme-instructed self-assembly system is widely used, but this approach typically has a small effect on cellular fate. In this study, we show that the intralysosomal assembly by a carbonic anhydrase IX (CAIX)-targeting peptide amphiphile (Pep-AT) can control cellular fate with a low therapeutic dose by tuning...

The treatment of osteosarcoma involves an adjuvant therapy that combines surgery and chemotherapy. However, considering that children are the main victims of osteosarcoma, replacing such a harsh treatment with a soft but powerful method that ensures a complete cure while having no adverse effects is highly desirable. To achieve this aim, we have de...

Intramitochondrial supramolecular assembly can be a new therapeutic strategy for treating cancer because mitochondria are the key for virtually all facets of the tumorigenesis. However, the in vivo applications of mitochondria‐targeting molecules are limited due to the positive charge and hydrophobicity that should be possessed by these molecules t...

Cellular senescence of the retinal pigment epithelium (RPE) is thought to play an important role in vision-threatening retinal degenerative diseases, such as age-related macular degeneration (AMD). However, the single-cell RNA profiles of control RPE tissue and RPE tissue exhibiting cellular senescence are not well known. We have analyzed the singl...

Mitochondria are essential intracellular organelles involved in many cellular processes, especially adenosine triphosphate (ATP) production. Since cancer cells require high ATP levels for proliferation, ATP elimination can be a unique target for cancer growth inhibition. We describe a newly developed mitochondria-targeting nucleopeptide (MNP) that...

For efficient drug delivery, stable encapsulation of a large amount of anticancer drugs is crucial, not to mention cell-specific delivery. Among many possible nanocarriers, mesoporous silica nanoparticles are versatile frameworks that satisfy those requirements owing to their characteristic internal pores with a large surface area and a tunable sur...

Laminaria japonica is a brown alga and is composed primarily of polysaccharides. Fucoidan and laminarin are the major polysaccharides of L. japonica and exhibit biological activities, including immune modulation and anti-coagulant and antioxidant effects in animals and humans. In this study, we evaluated the ability of fucoidan and laminarin from L...

Tunable Mesoporosity In article number 2107006, Chae Un Kim, Ja‐Hyoung Ryu, Myoung Soo Lah, and co‐workers synthesize a tunable mesoporous metal‐organic framework that can be used for enzymatic immobilization through heat treatment of highly mosaic crystals with low‐density crystallites through localized agglomeration of volume‐reduced crystallites...

Triphenylphosphonium derivatives induce mitochondrial dysfunction by inhibiting the respiratory chain, membrane depolarization, and generation of reactive oxygen species. However, the clinical application has been limited due to low aqueous solubility. In this regard, a series of novel mitochondria targeting agents were designed by introducing quat...

A new synthetic approach for tunable mesoporous metal–organic frameworks (MeMs) is developed. In this approach, mesopores are created in the process of heat conversion of highly mosaic metal–organic framework (MOF) crystals with non‐interpenetrated low‐density nanocrystallites into MOF crystals with two‐fold interpenetrated high‐density nanocrystal...

Cellular senescence, a stable form of cell cycle arrest, facilitates protection from tumorigenesis and aids in tissue repair as they accumulate in the body at an early age. However, long‐term retention of senescent cells causes inflammation, aging of the tissue, and progression of deadly diseases such as obesity, diabetes, and atherosclerosis. Vari...

Although age-related macular degeneration (AMD) is a multifactorial disorder with angiogenic, immune, and inflammatory components, the most common clinical treatment strategies are antiangiogenic therapies. However, these strategies are only applicable to neovascular AMD, which accounts for less than 20% of all AMD cases, and there are no FDA-appro...

Drug resistance is a major cause of treatment failure for small-molecule cancer chemotherapies, despite the advances in combination therapies, drug delivery systems, epigenetic drugs, and proteolysis-targeting chimeras. Herein, we report the use of a drug resistance-free cytotoxic nanodrug as an alternative to small-molecule drugs. The present nano...

Currently, there is no appropriate treatment option for patients with sorafenib-resistant hepatocellular carcinoma (HCC). Meanwhile, pronounced anticancer activities of newly-developed mitochondria-accumulating self-assembly peptides (Mito-FF) have been demonstrated. This study intended to determine the anticancer effects of Mito-FF against sorafen...

Controlled intracellular chemical reactions to regulate cellular functions remain a challenge in biology mimetic systems. Herein, we developed an intra-mitochondrial bio-orthogonal reaction to induce aggregation induced emission. In situ carbonyl ligation inside mitochondria drives the molecules to form nano-aggregates with green fluorescence, whic...

In a biological system, energy-consuming reactions to attain a biological dissipative state are ubiquitous, and mimicking such reactions is a great challenge in synthetic chemistry. Herein, we report an intra-mitochondrial polymerization strategy for constructing macroscopic structures using a reactive oxygen species (ROS)-dissipative system. This...

The intracellular or pericellular self-assembly of amphiphilic peptides is emerging as a potent cancer therapeutic strategy. Achieving self-assembly of amphiphilic peptides inside a cell or cellular organelle is challenging due to the complex cellular environment, which consists of many amphiphilic biomolecules that may alter the self-assembling pr...

Here, we provide the possibility of a novel chemotherapeutic agent against gastric cancer cells, comprising the combination of 5-fluorouracil (5-FU) and a mitochondria-targeting self-assembly peptide, which is a phenylalanine dipeptide with triphenyl phosphonium (Mito-FF). The anticancer effects and mechanisms of 5-FU and Mito-FF, individually or i...

The development of photosensitizers for cancer photodynamic therapy has been challenging due to their low photostability and therapeutic inefficacy in hypoxic tumor microenvironments. To overcome these issues, we have developed a mitochondria‐targeted photosensitizer consisting of an indocyanine moiety with triphenylphosphonium arms, which can self...

The design of peptide-based therapeutics is generally based on the replacement of L-amino acids with D-isomers to obtain improved therapeutic efficiency. However, D-isomers are expensive and frequently induce undesirable immune responses. In the present work, we demonstrate that an intra-mitochondrially self-assembling amphiphilic peptide exhibits...

The molecular chaperone TRAP1 is the mitochondrial paralog of Hsp90 and is overexpressed in many cancer cells. The orthosteric ATP-binding site of TRAP1 has been considered the primary inhibitor binding location, but TRAP1 allosteric modulators have not yet been investigated. Here, we generated and characterized the Hsp90 inhibitor PU-H71, conjugat...

Natural polymers with abundant side functionalities are emerging as a promising binder for high‐capacity yet large‐volume‐change silicon anodes with a strong and reversible supramolecular interaction that originates from secondary bonding. However, the supramolecular network solely based on hydrogen bonding is relatively vulnerable to repeated defo...

The mitochondrion is a dynamic eukaryotic organelle that controls lethal and vital functions of the cell. Being a critical center of metabolic activities and involved in many diseases, mitochondria have been attracting attention as a potential target for therapeutics, especially for cancer treatment. Structural and functional differences between he...

Nanoparticle-based targeted drug delivery system (DDS) is one of the major applications of nanotechnology in modern biomedical research. Basically, it comprises of bare or functionalized biocompatible nanoparticles with or without targeting ligands and one or more chemotherapeutic drugs. While the targeting efficacy of DDS without targeting ligands...

Mitochondria targeting sensitizers are continuing to gain importance in photodynamic therapy (PDT). Members of the 90 KDa heat shock protein (Hsp90) family, including TRAP1 (Hsp75), are overexpressed in cancer cells...

Nanomedicines exploit the unusual physicochemical and biological properties of nanoparticles, including their nanoscopic size, high surface‐area‐to‐volume ratio, easy surface modification, and biocompatibility. Among various therapeutic and diagnostic applications of nanomedicines, cancer‐targeted drug delivery systems (DDS) have been found to be a...

Self-assembly of peptides containing both L and D isomers often results in nanostructures with enhanced properties compared to their enantiomeric analogues, such as faster kinetics of formation, higher mechanical strength, and enzymatic stability. However, occurrence and consequences of the heterochiral assembly in the cellular microenvironment is...

Despite the extended use of cationic gold nanoparticles (AuNPs) in biomedical applications, direct one-pot synthesis of AuNPs with tunable size in aqueous media is limited due to the deleterious electrostatic attraction between AuCl4-anions and positively charged ligands. This paper describes the one-pot synthesis of cationic gold nanoparticles wit...

Metal-Organic Framework (MOFs) nanoparticles with high porosity and greater tunability have emerged as new drug delivery vehicles. However, premature drug release still remains a challenge in MOF delivery system. Here, we report enzyme responsive polymer coated MOF gatekeeper system using hyaluronic acid (HA) and PCN-224 nanoMOF. The external surfa...

The intracellular delivery efficiency of drug-loaded nanocarriers is often limited by biological barriers arising from the plasma membrane and the cell interior. In this work, the entering of doxorubicin (Dox)-loaded mesoporous silica nanoparticles (MSNs) into cytoplasm was acoustically enhanced through direct penetration with the assistance of hyp...

Pluronic F127 forms spherical micelle with a defined number of molecules aggregated in aqueous environments. Such self-assembled micelles dissociate into unimers below certain concentration and temperature. We stabilized the micelles by semi-interpenetrating network (sIPN) formation within the hydrophobic core in the presence of a fluorescent dye....

Smart drug delivery in a site-specific and time-controlled manner is critical for reducing drug side effects while maximizing therapeutic efficacy. Herein, we describe an efficient approach to control the degradation kinetics of polyether micelles under acidic conditions using random copolymers of functional epoxide monomers bearing different aceta...

Targeted drug delivery using nanoparticles can minimize the side effects of conventional pharmaceutical agents and enhance their efficacy. However, translating nanoparticle-based agents into clinical applications still remains a challenge due to the difficulty in regulating interactions on the interfaces between nanoparticles and biological systems...

Protein detection and identification are important for the diagnosis of diseases; however, the development of facile sensing probes still remains challenging. Here, we present an array-based “turn on” protein-sensing platform capable of detecting and identifying proteins using aggregation-induced emission luminogens (AIEgens). The water-soluble AIE...

Current drug delivery systems are hampered by poor delivery to tumors, in part reflecting poor encapsulation stability of nanocarriers. Although nanocarriers such as polymeric micelles have high colloidal stability and do not aggregate or precipitate in bulk solution, nanocarriers with low encapsulation stability can lose their cargo during circula...

Systemic administration of mesoporous silica nanoparticles (MSNs) in biomedical applications has recently been questioned due to their poor degradability, which is necessary for the successful development of new drug delivery systems. Herein, we report the development of colloidal state-degradable MSNs functionalized with versatile polymer-gatekeep...

Owing to the unique advantages of combining the characteristics of hydrogels and nanoparticles, nanogels are actively investigated as a promising platform for advanced biomedical applications. In this work, a self-cross-linked hyperbranched polyglycerol nanogel is synthesized using the thiol–disulfide exchange reaction based on a novel disulfide-co...

The usage of biomineralization that regulates cellular functions has emerged as a potential therapeutic tool. However, the lack of selectivity still limits its therapeutic efficacy. Here, we report a subcellular-targeting biomineralization system featuring triphenylphosphonium cation (TPP) (mitochondria-targeting moiety) and trialkoxysilane (mitoch...

A combinatorial treatment comprising thermal therapy and chemotherapy offers synergistic effects by inducing localized heat to targeted tumor sites and simultaneously delivering anticancer drugs to minimize systemic side effects and enhance the cytotoxic effect. In this study, a novel platform is developed for combining photothermal therapy and che...

Achieving spatiotemporal control of molecular self-assembly associated with actuation of biological functions inside living cells remains a challenge owing to the complexity of the cellular environments and the lack of characterization tools. We present, for the first time, the organelle-localized self-assembly of a peptide amphiphile as a powerful...

Mitochondria-targeted cancer therapies have proven to be more effective than other similar non-targeting techniques, especially in photodynamic therapy (PDT). Indocyanine dye derivatives, particularly IR-780 are widely known for their PDT utility. However, poor water solubility, dark toxicity, and photobleaching are limiting factors of these dyes,...

Despite the growing interest in amphiphilic block copolymers for the application in micelles as ideal drug delivery carriers, there remain some challenges related to biocompatibility, stability, degradability, and loading efficiency of the micelles. Herein, we report a novel hydrophobic, pH-responsive epoxide monomer, tetrahydropyranyl glycidyl eth...

Combination chemotherapy has become the primary strategy against cancer multidrug resistance; however, accomplishing optimal pharmacokinetic delivery of multiple drugs is still challenging. Herein, we report a sequential combination drug delivery strategy exploiting a pH-triggerable and redox switch to release cargos from hollow silica nanoparticle...

Correction for 'Externally controlled drug release using a gold nanorod contained composite membrane' by Kibeom Kim, et al., Nanoscale, 2016, 8, 11949-11955.

Versatile drug delivery devices using nanoporous membranes consisting of gold nanorods and dendrimers have been demonstrated to provide light-triggered on-demand pulsatile release from a reservoir containing highly enriched therapeutics for a real patient's needs. The drug release rate is directly correlated with the temperature increase and irradi...

A simple peptide based prodrug of camptothecin (CPT) has been synthesised in which the CPT is conjugated to a tripeptide (KCK) via a disulfide linkage (KCK-CPT) and self-assembled into well-defined nanostructures in water depending on the concentration. The hyaluronic acid (HA) complex of KCK-CPT exhibited target specific toxicity with excellent an...

The electrochemical performance of Li-ion batteries (LIBs) can be highly tuned by various factors including the morphology of the anode material, the nature of the electrolyte, the binding material, and the percentage of conducting materials. Binding materials have been of particular interest to researchers over decades as a means to further improv...

Advances in water-insoluble drug delivery systems are limited by selective delivery, loading capacity, and colloidal and encapsulation stability. We have developed a simple and robust hydrophobic-drug delivery platform with different types of hydrophobic chemotherapeutic agents using a noncovalent gatekeeper's technique with mesoporous silica nanop...

Formation of both mechanically durable and programmably degradable layer-by-layer (LbL) films in a biocompatible fashion has potential applications in cell therapy, tissue engineering, and drug-delivery systems, where the films are interfaced with living cells. In this work, we developed a simple but versatile method for generating in situ cross-li...

The mitochondrial pool of Hsp90 and its mitochondrial paralog, TRAP1, suppresses cell death and reprograms energy metabolism in cancer cells; therefore, Hsp90 and TRAP1 have been suggested as target proteins for anticancer drug development. Here, we report that the actual target protein in cancer cell mitochondria is TRAP1, and current Hsp90 inhibi...

Selective targeting of tumor cells and release of drug molecules inside the tumor microenvironment can reduce the adverse side effects of traditional chemotherapeutics because of the lower dosages required. This can be achieved by using stimuli-responsive targeted drug delivery systems. In the present work, a robust and simple one-pot route is deve...

This work demonstrates the design, synthesis, characterization and study on electrochemical performance of a novel binder for silicon (Si) anode in lithium ion batteries (LIBs). The polymeric binder with three different functional groups such as carboxylic acid (COOH), carboxylate (COO-) and hydroxyl (OH), in a single polymer backbone has been synt...

Supramolecular nanogel, a physically cross-linked nanosize hydrogel, spontaneously self-assembles in aqueous solution via secondary interactions and is thus of great interest in nanomedicine as a drug carrier. We developed a versatile method for supramolecular nanogel self-assembled by electrostatic interaction between positive surfactant micelles...

Influence of Hofmeister ions has been investigated on the size and guest encapsulation stability of a polymeric nanogel. While variations in macroscopic phase transitions have been observed in response to the presence of salts, changes in the size and host-guest behavior of polymeric aggregates in the presence of salts have not been explored in any...

Bent-shaped rigid-core molecules with flexible chiral dendrons grafted to the outer side of the bend were synthesized and characterized by circular dichroism, differential scanning calorimetry, X-ray scatterings, and transmission electron microscopy in solution and the solid state. The bent aromatic rods based on hepta- and nonaphenylene with nitri...

We demonstrate the self-assembly of tripeptide amphiphiles into spherical hollow capsules from linear nanoribbons via control of the molecular packing. We achieved a transition of arrangement from anisotropic to isotropic by an elaborate design of the molecular architecture.

Supramolecular nanoassemblies, which are capable of binding and delivering either lipophilic small molecules or hydrophilic molecules, are of great interest. Concurrently binding and delivering this combination of molecules is cumbersome, because of the opposing supramolecular host requirements. We describe the development of a versatile nanoassemb...

Nanoscale vehicles for delivery have been of interest and extensively studied for two decades. However, the encapsulation stability of hydrophobic drug molecules in delivery vehicles and selective targeting these vehicles into disease cells are potential hurdles for efficient delivery systems. Here we demonstrate a simple and fast synthetic protoco...

Nanoscopic vehicles that stably encapsulate drug molecules and release them in response to a specific trigger are of great interest due to implications in therapeutic applications, especially for cancer therapy. For this purpose, we have synthesized highly stable polymeric nanogels, in which the kinetics of guest molecule release can be fine-tuned...

Exchange dynamics of lipophilic guest molecules, encapsulated in supramolecular nanoassemblies in aqueous solutions, have implications in evaluating the stability of drug delivery vehicles. This is because exchange dynamics is related to the propensity of a nanocarrier to be leaky. We describe a fluorescence resonance energy transfer (FRET) based m...

The stability of encapsulation in self-assembly systems is limited during blood circulation because of a requisite concentration for assembly formation. For deliberate molecular design for stable encapsulation, targeting, and triggered release, we have developed a facile synthetic method for highly stable, polymeric nanogels using a simple intra/in...

Amphiphilic polymers of different hydrophilic-lipophilic ratios were prepared by free radical polymerization using two monomers consisting of triethylene glycol as the hydrophilic part and an alkyl chain connected by disulfide bond as the hydrophobic part. These polymers form micelle-like nanoassemblies in aqueous media and can encapsulate hydropho...

We have prepared functionalized nanoporous thin films from a polystyrene-block-polyethylene oxide block copolymer, which was made cleavable due to the intervening disulfide bond. The cleavage reaction of the disulfide bond leaves behind free thiol groups inside the nanopores of polystyrene thin film. This nanoporous thin film can be used as a templ...

Self-assembling rigid-flexible block molecules consisting of a laterally extended aromatic segment and different lengths of hydrophilic coils were synthesized and characterized. The block molecule based on a long poly(ethylene oxide) coil (1), in the melt state, shows an unidentified columnar structure, whereas the molecule with a shorter poly(ethy...

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One of the most fascinating subjects in areas such as nanoscience and biomimetic chemistry is concerned with the construction of novel supramolecular nanoscopic architectures with well defined shapes and functions. Supramolecular assemblies of aromatic rod molecules provide a facile entry into this area. Aromatic rigid rod molecules consisting of h...

Chiral-bridged rod molecules (CBRs) that consisted of bis(penta-p-phenylene) conjugated to an opened or closed chiral bridging group as a rigid segment and oligoether dendrons as flexible segments were synthesized and characterized. In the bulk state, both molecules self-assemble into a hexagonal columnar structure, as confirmed by X-ray scattering...

The dumbbell-shaped aromatic amphiphilic molecules consisting of hexa-p-phenylene-conjugated carbazole moieties on both ends as a rigid rod segment and oligoether chains with different cross-sections (i.e., linear branch (1), dibranch (2), and tetrabranch (3)) attached to a carbazole as flexible chains were synthesized and their self-assembling beh...

Carbohydrate-attached nanostructures… … have been utilized in studies into the agglutination and motility inhibition of pathogenic cells for potential applications in pathogen capture, inactivation, and detection. Fiberlike nanostructures such as carbon nanotubes and β-sheet peptide nanoribbons are especially suitable for aggregating cells. In thei...

We explored a method of controlling bacterial motility and agglutination by using self-assembled carbohydrate-coated beta-sheet nanoribbons. To this aim, we synthesized triblock peptides that consist of a carbohydrate, a polyethylene glycol (PEG) spacer, and a beta-sheet-forming peptide. An investigation into the effect of PEG-spacer length on the...

The development of novel supramolecular materials with nanometer-scale architectures and the effect of these architectures on the materials' properties are currently of great interest in molecular design. Liquid crystalline assemblies of rod-like mesogenic molecules containing flexible coils (rod–coil molecules) provide afacile entry into this area...

We have demonstrated that rod-coil molecules based on a tetra-p-phenylene rod and a poly(propylene oxide) coil self-assemble into an unprecedented body centered cubic micellar structure in the melt, through detailed morphological analysis by X-ray scattering and transmission electron microscopy experiments.

We demonstrate here the rational design strategy to control the length of 1-dimensional beta-sheet peptide nanoassembly. We synthesized the beta-sheet peptides with attached coils and carbohydrates. We reasoned that the bulkiness of the coils affects the final length of the assembled beta-sheet peptide nanostructures because of the steric crowding...