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Featured researches published by DaeYong Lee.


Journal of Controlled Release | 2017

Bioreducible branched poly(modified nona-arginine) cell-penetrating peptide as a novel gene delivery platform

Jisang Yoo; DaeYong Lee; Vipul Gujrati; N. Sanoj Rejinold; Kamali Manickavasagam Lekshmi; Saji Uthaman; Chanuk Jeong; In-Kyu Park; Sangyong Jon; Yeu-Chun Kim

Abstract Cell‐penetrating peptides (CPPs) have been widely used to deliver nucleic acid molecules. Generally, CPPs consisting of short amino acid sequences have a linear structure, resulting in a weak complexation and low transfection efficacy. To overcome these drawbacks, a novel type of CPP is required to enhance the delivery efficacy while maintaining its safe use at the same time. Herein, we report that a bioreducible branched poly‐CPP structure capable of responding to reducing conditions attained both outstanding delivery effectiveness and selective gene release in carcinoma cells. Branched structures provide unusually strong electrostatic attraction between DNA and siRNA molecules, thereby improving the transfection capability through a tightly condensed form. We designed a modified type of nona‐arginine (mR9) and synthesized a branched‐mR9 (B‐mR9) using disulfide bonds. A novel B‐mR9/pDNA polyplex exhibited redox‐cleavability and high transfection efficacy compared to conventional CPPs, with higher cell viability as well. B‐mR9/VEGF siRNA polyplex exhibited significant serum stability and high gene‐silencing effects in vitro. Furthermore, the B‐mR9 polyplex showed outstanding tumor accumulation and inhibition ability in vivo. The results suggest that the bioreducible branched poly CPP has great potential as a gene delivery platform. Graphical abstract Figure. No Caption available.


RSC Advances | 2015

Establishment of a controlled insulin delivery system using a glucose-responsive double-layered nanogel

DaeYong Lee; Ki Baek Choe; YongJun Jeong; Jisang Yoo; Sung Mun Lee; Ji-Ho Park; Pilhan Kim; Yeu-Chun Kim

Glucose-responsive insulin delivery systems have been proposed as a promising alternative to conventional intramuscular administration methods, which causes low patient compliance due to the requirement of multiple administration. In addition, protein-based glucose-responsive systems using glucose oxidase and lectin have not achieved success in clinical trials because of their low biostability and potential cytotoxicity. In order to overcome these issues, the phenylboronic acid (PBA)-derivatives converted to hydrophilic moieties with an elevated glucose level play a key role in controlled insulin delivery systems due to their better biostability and high biocompatibility. In order to endow glucose-responsiveness to insulin delivery carriers using PBA derivatives, a glycol chitosan (GC)/sodium alginate (SA)-poly(L-glutmate-co-N-3-L-glutamylphenylboronic acid) (PGGA) graft polymer double-layered nanogel is synthesized by N-carboxyanhydride (NCA) polymerization and carbodiimide coupling reactions. The GC/SA-PGGA double-layered nanogel controllably releases insulin at diabetic glucose levels in vitro, and shows high biocompatibility, determined by cell viability and a hemolysis assay. Moreover, controlled insulin release at high glucose levels can be accomplished using the GC/SA-PGGA double-layered nanogel in mouse studies. Therefore, the GC/SA-PGGA double-layered nanogel characterized by glucose-sensitivity and superior biocompatibility may act as a potential platform for advanced insulin delivery systems.


Journal of Controlled Release | 2017

Protease-activatable cell-penetrating peptide possessing ROS-triggered phase transition for enhanced cancer therapy

Jisang Yoo; N. Sanoj Rejinold; DaeYong Lee; Sangyong Jon; Yeu-Chun Kim

&NA; Reactive oxygen species (ROS)‐ or protease‐responsive materials have been utilized as carriers in cancer therapies because ROS and specific proteases are overproduced in cancer cells. Methionine‐based polypeptides containing a thioether group are promising candidates due to their ROS‐responsiveness which provides a phase transition. Herein, we developed protease‐activatable cell‐penetrating peptide containing a ROS‐responsive methionine, a cell permeable lysine chain, and a matrix metalloproteinase (MMP)‐cleavable linker. We designed a poly(l‐methionine‐block‐l‐lysine)‐PLGLAG‐PEG (MLMP) and doxorubicin (DOX) was loaded into the micelle core. The MLMP exhibited MMP‐sensitive cleavage and ROS‐induced DOX release. Moreover, we confirmed efficient DOX delivery into cancer cells and induction of the apoptotic capability in vitro. In a bio‐distribution study, IR‐780 dye encapsulated MLMP showed superior tumor targetability with long retention. Furthermore, MLMP (DOX) exhibited outstanding tumor inhibition capability with non‐toxicity compared to free DOX, indicating that dual stimuli‐MLMP has great potential as an anticancer drug delivery platform. Graphical abstract Figure. No caption available.


Acta Biomaterialia | 2017

pH-controllable cell-penetrating polypeptide that exhibits cancer targeting

DaeYong Lee; Ilkoo Noh; Jisang Yoo; N. Sanoj Rejinold; Yeu-Chun Kim

Helical peptides were naturally-occurring ordered conformations that mediated various biological functions essential for biotechnology. However, it was difficult for natural helical polypeptides to be applied in biomedical fields due to low bioavailability. To avoid these problems, synthetic alpha-helical polypeptides have recently been introduced by further modifying pendants in the side chain. In spite of an attractive biomimetic helical motif, these systems could not be tailored for targeted delivery mainly due to nonspecific binding events. To address these issues, we created a conformation-transformable polypeptide capable of eliciting a pH-activated cell-penetrating property solely at the cancer region. The developed novel polypeptide showed that the bare helical conformation had a function at physiological conditions while the pH-induced helical motif provided an active cell-penetrating characteristic at a tumor extracellular matrix pH. The unusual conformation-transformable system can elicit bioactive properties exclusively at mild acidic pH. STATEMENT OF SIGNIFICANCE We developed pH-controllable cell-penetrating polypeptides (PCCPs) undergoing pH-induced conformational transitions. Unlike natural cell-penetrating peptides, PCCPs was capable of penetrating the plasma membranes dominantly at tumor pH, driven by pH-controlled helicity. The conformation of PCCPs at neutral pH showed low helical propensity because of dominant electrostatic attractions within the side chains. However, the helicity of PCCPs was considerably augmented by the balance of electrostatic interactions, thereby inducing selective cellular penetration. Three polypeptides undergoing different conformational transitions were prepared to verify the selective cellular uptake influenced by their structures. The PCCP undergoing low-to-high helical conformation provided the tumor specificity and enhanced uptake efficiency. pH-induced conformation-transformable polypeptide might provide a novel platform for stimuli-triggered targeting systems.


Journal of Controlled Release | 2017

Conformation-switchable helical polypeptide eliciting selective pro-apoptotic activity for cancer therapy

DaeYong Lee; Soo-Hwan Lee; Youjin Na; Ilkoo Noh; JongHoon Ha; Jisang Yoo; Hyun Bae Bang; Jong Hyun Park; Ki Jun Jeong; Chae-Ok Yun; Yeu-Chun Kim

&NA; Artificial cationic helical peptides possess an enhanced cell‐penetrating property. However, their cell‐penetrability is not converted by cellular environmental changes resulting in nonspecific uptake. In this study, pH‐sensitive anion‐donating groups were added to a helical polypeptide to simultaneously achieve tumor targeting and pro‐apoptotic activity. The mitochondria‐destabilizing helical polypeptide undergoing pH‐dependent conformational transitions selectively targeted cancer cells consequently disrupting mitochondrial membranes and subsequently inducing apoptosis. This work presents a promising peptide therapeutic system for cancer therapy. Graphical abstract Mitochondria‐destabilizing helical polypeptide undergoing a pH‐activated conformational transition selectively perturbed the mitochondrial outer membranes thereby inducing pro‐apoptosis. Figure. No caption available.


Advanced Science | 2018

Enhanced Photodynamic Cancer Treatment by Mitochondria‐Targeting and Brominated Near‐Infrared Fluorophores

Ilkoo Noh; DaeYong Lee; Heegon Kim; Chanuk Jeong; Yunsoo Lee; Jungoh Ahn; Hoon Hyun; Ji-Ho Park; Yeu-Chun Kim

Abstract A noninvasive and selective therapy, photodynamic therapy (PDT) is widely researched in clinical fields; however, the lower efficiency of PDT can induce unexpected side effects. Mitochondria are extensively researched as target sites to maximize PDT effects because they play crucial roles in metabolism and can be used as cancer markers due to their high transmembrane potential. Here, a mitochondria targeting photodynamic therapeutic agent (MitDt) is developed. This photosensitizer is synthesized from heptamethine cyanine dyes, which are conjugated or modified as follows. The heptamethine meso‐position is conjugated with a triphenylphosphonium derivative for mitochondrial targeting, the N‐alkyl side chain is modified for regulation of charge balance and solubility, and the indolenine groups are brominated to enhance reactive oxygen species generation (ROS) after laser irradiation. The synthesized MitDt increases the cancer uptake efficiency due to the lipo‐cationic properties of the triphenylphosphonium, and the PDT effects of MitDt are amplified after laser irradiation because mitochondria are susceptible to ROS, the response to which triggers an apoptotic anticancer effect. Consequently, these hypotheses are demonstrated by in vitro and in vivo studies, and the results indicate strong potential for use of MitDts as efficient single‐molecule‐based PDT agents for cancer treatment.


Polymers | 2018

Stimuli-Responsive Polypeptides for Biomedical Applications

DaeYong Lee; N. Rejinold; Seong Jeong; Yeu-Chun Kim

Stimuli-responsive polypeptides have gained attention because desirable bioactive properties can be easily imparted to them while keeping their biocompatibility and biodegradability intact. In this review, we summarize the most recent advances in various stimuli-responsive polypeptides (pH, reduction, oxidation, glucose, adenosine triphosphate (ATP), and enzyme) over the past five years. Various synthetic strategies exploited for advanced polypeptide-based materials are introduced, and their applicability in biomedical fields is discussed. The recent polypeptides imparted with new stimuli-responsiveness and their novel chemical and physical properties are explained in this review.


Journal of Industrial and Engineering Chemistry | 2017

Polypeptide-based polyelectrolyte complexes overcoming the biological barriers of oral insulin delivery

YongJun Jeong; DaeYong Lee; Kibaek Choe; Hyeji Ahn; Pilhan Kim; Ji-Ho Park; Yeu-Chun Kim


Biomaterials Research | 2016

A branched TAT cell-penetrating peptide as a novel delivery carrier for the efficient gene transfection

Chanuk Jeong; Jisang Yoo; DaeYong Lee; Yeu-Chun Kim


Journal of Industrial and Engineering Chemistry | 2018

Cancer-specific pro-oxidant therapy using low-toxic polypeptide micelles encapsulating piperlongumine

Eun Ji Hong; DaeYong Lee; Han Chang Kang; Yeu-Chun Kim; Min Suk Shim

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N. Sanoj Rejinold

Amrita Institute of Medical Sciences and Research Centre

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Hoon Hyun

Chonnam National University

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