Min Shim - Academia.edu (original) (raw)

Poster by Min Shim

Papers by Min Shim

The American Journal of Cardiology, 2015

There have been several reports showing that the statin use is associated with new-onset diabetes... more There have been several reports showing that the statin use is associated with new-onset diabetes mellitus (DM). The aim of the present study was to evaluate the impact of chronic statin use on development of new-onset DM in a series of Asian population. The patients were retrospectively enrolled using the electronic database of Korea University Guro Hospital from January 2004 to February 2010. A total of 10,994 patients without a history of diabetes were analyzed. Baseline lipid profiles, fasting glucose, Hemoglobin (Hb) A1c, and glucose tolerance tests were measured in all patients before statin treatment. Included patients had HbA1c ≤5.7% and fasting glucose level ≤100 (mg/dl). The patients were divided into 2 groups according to the use of statins (the statin group, n = 2,324 patients and the nonstatin group, n = 8,670 patients). To adjust baseline potential confounders, a propensity score-matched analysis was performed using logistic regression model. After propensity score matching, 2 propensity-matched groups (1,699 pairs, n = 3,398, C statistic = 0.859) were generated and analyzed. After propensity score matching, baseline characteristics of both groups were balanced except that the statin group was older and had higher rate of coronary artery disease compared with the nonstatin group. During a 3-year follow-up, the statin group had higher incidence of new-onset DM compared with the nonstatin group (hazard ratio 1.99, 95% CI 1.36 to 2.92, p <0.001), but the statin group showed lower incidence of major adverse cerebral-cardiovascular events compared with the nonstatin group (hazard ratio 0.40, 95% CI 0.19 to 0.85, p <0.001). In the present study, although the use of statins was associated with higher rate of new-onset DM, it markedly improved 3-year cardiovascular outcomes in Asian population.

Advanced Drug Delivery Reviews, 2015

The dynamic and versatile nature of diseases such as cancer has been a pivotal challenge for deve... more The dynamic and versatile nature of diseases such as cancer has been a pivotal challenge for developing efficient and safe therapies. Cancer treatments using a single therapeutic agent often result in limited clinical outcomes due to tumor heterogeneity and drug resistance. Combination therapies using multiple therapeutic modalities can synergistically elevate anti-cancer activity while lowering doses of each agent, hence, reducing side effects. Co-administration of multiple therapeutic agents requires a delivery platform that can normalize pharmacokinetics and pharmacodynamics of the agents, prolong circulation, selectively accumulate, specifically bind to the target, and enable controlled release in target site. Nanomaterials, such as polymeric nanoparticles, gold nanoparticles/cages/shells, and carbon nanomaterials, have the desired properties, and they can mediate therapeutic effects different from those generated by small molecule drugs (e.g., gene therapy, photothermal therapy, photodynamic therapy, and radiotherapy). This review aims to provide an overview of developing multi-modal therapies using nanomaterials ("combo" nanomedicine) along with the rationale, up-to-date progress, further considerations, and the crucial roles of interdisciplinary approaches.

Objectives: This paper aims to explain principles of gist-based health message design and discuss... more Objectives: This paper aims to explain principles of gist-based health message design and discuss their implications for health promotion and public health education. Methods: After reviewing Reyna and Brainerd's Fuzzy Trace Theory(FTT), the authors explicate how to transform FTT into a practical guidance of health message design. Our explication is based upon FTT's reasoning that human intuition, rather than analysis, takes a primary role in message recall and comprehension, followed by judgment and decision making. We expect gist-based message design to be appropriate to serve such intuition. Results: Four principles of gist-based message design are offered: (1) provision of qualitative, as well as quantitative, information of gist, (2) inclusion of visual images corresponding to gist, (3) use of effective message formats to emphasize the gist (4) inclusion of relevant reasons and contextutal information. Conclusions: Gist-based message design has theoretical and practical...

Hyperspectral cameras acquire reflectance values at many different wavelength bands. Dimensions t... more Hyperspectral cameras acquire reflectance values at many different wavelength bands. Dimensions tend to increase because spectral information is stored in each pixel. Several attempts have been made to reduce dimensional problems such as the feature selection using Adaboost and dimension reduction using the Simulated Annealing technique. We propose a novel material detection method that consists of four steps: feature band selection, feature extraction, SVM (Support Vector Machine) learning, and target and specific region detection. It is a combination of the band ratio method and Simulated Annealing algorithm based on detection rate. The experimental results validate the effectiveness of the proposed feature selection and band ratio method.

We proposed a first person shooter for both hands with multiple mouse devices, which are not used... more We proposed a first person shooter for both hands with multiple mouse devices, which are not used in existing games. Players control their movement and shooting separately using dual guns for both hands. For two-hand usage, we designed a display method for multiple mouse pointers. First, we loaded typical physical driver into the memory and registered our developed multiple mouse device driver instead of the existing MS Windows device driver. We then executed both message loop procedures for Windows mouse event handling and those for multiple mouse event handling. We could display multiple mouse cursor images and utilize both mouse devices separately. After that, a prototype game using both hands was developed for an experimental study.

RSC Adv., 2015

ABSTRACT To produce artificial psychological feeling, especially ‘pain’, electrical mimic structu... more ABSTRACT To produce artificial psychological feeling, especially ‘pain’, electrical mimic structure of human skin has been studied. Touch by a sharp and a blunt object induce figurative different deformations of the skin of human fingers. Imitating this phenomenon, the skin mimic device employing the piezoelectric nanowire sensor arrays can generate the electrical ‘pain’ signal with signal processing when a pen cap presses the device. The electrical ‘pain’ signal is expected to enhance the protection mechanism of android robot or mobile phone from harsh environment.

Neuroscience, Jan 4, 2015

Trigeminal ganglia (TG) contain neuronal cell bodies surrounded by satellite glial cells. Althoug... more Trigeminal ganglia (TG) contain neuronal cell bodies surrounded by satellite glial cells. Although peripheral injury is well known to induce changes in gene expression within sensory ganglia, detailed mechanisms whereby peripheral injury leads to gene expression within sensory ganglia are not completely understood. Reactive oxygen species (ROS) are an important modulator of hyperalgesia, but the role of ROS generated within sensory ganglia is unclear. Since ROS are known to affect transcription processes, ROS generated within sensory ganglia could directly influence gene expression and induce cellular changes at the soma level. In this study, we hypothesized that peripheral inflammation leads to cytokine and chemokine production and ROS generation within TG and that transient receptor potential melastatin (TRPM2), a well known oxidative sensor, contributes to ROS-induced gene regulation within TG. The masseter injection of complete Freund's adjuvant (CFA) resulted in a significa...

2012 IEEE International Conference on Automation Science and Engineering (CASE), 2012

ABSTRACT It is important to stably extract horizon lines for sea-based infrared search and track.... more ABSTRACT It is important to stably extract horizon lines for sea-based infrared search and track. Most of the existing solutions for the problems only use single image to detect horizon line. Although this results in good accuracy for some images, it often fails to detect horizons in foggy, occluded environments. In this paper, we propose a novel horizon detection and tracking method that is robust to sensor vibrations and occlusions using image and sensor-based initial horizon detection and robust statistics. Local horizon optimization and tracking produce stable horizons in occluded environments. The experimental results validate the robustness of the proposed method in real infrared images.

Biomater. Sci., 2014

ABSTRACT Development of efficient carriers for small interfering RNA (siRNA) delivery and validat... more ABSTRACT Development of efficient carriers for small interfering RNA (siRNA) delivery and validation tools for assessing in vivo RNA interference (RNAi) efficiency is crucial to advance RNAi-based therapeutics to the clinic. Here, acid-degradable ketalized linear polyethylenimine (KL-PEI) designed for efficient, stimuli-responsive, and biocompatible siRNA delivery was used to complex with GFP-silencing siRNA (GFP siRNA) for in vivo RNAi. The in vivo gene silencing efficiency of GFP siRNA/KL-PEI polyplexes was evaluated at mRNA, protein, and histological levels using a mouse bearing a GFP-expressing tumor. Intravenously injected GFP siRNA/KL-PEI polyplexes significantly reduced GFP expression in tumors and whole blood of mice, depending on the dosage of GFP siRNA and the time course. Average GFP mRNA levels in the tumors of siRNA/KL-PEI polyplex-injected mice were also reduced. The described siRNA carriers and RNAi validation methodologies in this study may provide insightful clues for the development of RNAi-based therapeutics and preclinical trials.

Algorithms and Technologies for Multispectral, Hyperspectral, and Ultraspectral Imagery XIX, 2013

ABSTRACT This paper presents a concealed target detection based on the intersection kernel Suppor... more ABSTRACT This paper presents a concealed target detection based on the intersection kernel Support Vector Machine (SVM). Hyperspectral imagers are widely used in the field of target detection and material analysis. In military applications, it can be used to border protection, concealed target detection, reconnaissance and surveillance. If disguised enemies not detected in advance, the damage of allies will be catastrophic by unexpected attack. Concealed object detection using radar and terahertz method is widely used. However, these active techniques are easily exposed to the enemy. Electronic Optical Counter Counter Measures (EOCCM) using hyperspectral imagers can be a feasible solution. We use the band selected feature directly and the intersection kernel based SVM. Different materials show different spectrums although they look similar in CCD camera. We propose novel concealed target detection method that consist of 4 step, Feature band selection, Feature Extraction, SVM learning and target detection.

Polymer Chemistry, 2012

ABSTRACT Stimuli-triggered degradation and facilitated intracellular release of nucleic acids are... more ABSTRACT Stimuli-triggered degradation and facilitated intracellular release of nucleic acids are key design factors in developing efficient and biocompatible nonviral gene carriers. In this study, a cationic polymer was developed with aims to achieve enhanced gene transfection and low cytotoxicity via rapid biodegradation and subsequent intracellular de-complexation in response to dual stimuli in a cell. Diaminoethane was polymerized to synthesize cationic and hydrolytically degradable poly(amino ester), and then it was further conjugated with acid-degradable amino ketal branches. The resulting polymer, ketalized poly(amino ester) (K-PAE), differentially degrades via rapid hydrolysis of the ketal branches in the mildly acidic endosome and subsequent gradual degradation of the polyester backbone in the cytoplasm. DNA/K-PAE polyplexes underwent acid-triggered de-complexation at an endosomal pH, leading to efficient intracellular release of DNA and significantly enhanced transfection efficiency. In addition, DNA/K-PAE polyplexes demonstrated low cytotoxicity and serum-resistant gene transfection, in comparison with commercial counterpart polymers, promising for efficient and safe gene delivery in vivo. This study presents insightful design clues for developing efficient, versatile, stimuli-responsive, and biocompatible polymers for nonviral gene delivery.

Nanomedicine: Nanotechnology, Biology and Medicine, 2014

Nano-enabled drug delivery (NEDD) systems are rapidly emerging as a key area for nanotechnology a... more Nano-enabled drug delivery (NEDD) systems are rapidly emerging as a key area for nanotechnology application. Understanding the status and developmental prospects of this area around the world is important to determine research priorities, and to evaluate and direct progress. Global research publication and patent databases provide a reservoir of information that can be tapped to provide intelligence for such needs. Here, we present a process to allow for extraction of NEDD-related information from these databases by involving topical experts. This process incorporates in-depth analysis of NEDD literature review papers to identify key subsystems and major topics. We then use these to structure global analysis of NEDD research topical trends and collaborative patterns, inform future innovation directions. This paper describes the process of how to derive nano-enabled drug delivery-related information from global research and patent databases in an effort to perform comprehensive global analysis of research trends and directions, along with collaborative patterns.

Microscopy Research and Technique, 2010

Elucidating dynamic morphological changes of gene-carrying vectors and their nucleic acid release... more Elucidating dynamic morphological changes of gene-carrying vectors and their nucleic acid release under varying intracellular conditions has been a technical challenge. Atomic force microscopy (AFM) was used to observe nucleic acid/polymer polyplexes under endosomal and reducible cytosolic conditions. Both ketalized (acid-degradable) and unmodified (nondegradable) polyethylenimine (PEI) in linear and branched forms were used to prepare plasmid DNA- or siRNA-complexing polyplexes. Then, the polyplexes' complexation and disassembly were observed by in situ AFM in various differentially changing buffers that represent intracellular conditions. Results demonstrated obvious morphological destruction of DNA/ketalized linear PEI (KL-PEI) polyplexes under mildly acidic endosomal conditions, whereas no morphological changes were observed by DNA/ketalized branched PEI (KB-PEI) under the same conditions. In addition, siRNA was more efficiently dissociated from KL-PEI than KB-PEI under the same conditions. Nondegradable PEI did not show any evidence that DNA or siRNA was released. Anionic biomacromolecules (e.g., heparan sulfate), which was hypothesized to dissociate nucleic acids from cationic polymers, did not successfully disassemble polyplexes but appeared to be adsorbed on cationic polymers. The in situ AFM results combined with in vitro cellular transfection and gene silencing indicated that efficient endosomal escape of plasmid DNA in a compact polyplex form is required for efficient gene expression. On the contrary, rapid dissociation of siRNA from its cationic carrier is crucial for efficient gene silencing. The findings of this study may provide new insightful information for designing stimuli-responsive nonviral gene vectors as well as expanding tools for investigating nonviral vectors in nanoscales under biologically inspired conditions.

Lab on a Chip, 2006

To elaborate on the applicability of the electrokinetic micro power generation, we designed and f... more To elaborate on the applicability of the electrokinetic micro power generation, we designed and fabricated the silicon-glass as well as the PDMS-glass microfluidic chips with the unique features of a multi-channel. Besides miniaturizing the device, the key advantage of our microfluidic chip utilization lies in the reduction in water flow rate. Both a distributor and a collector taking the tapered duct geometry are positioned aiming the uniform distribution of water flow into all individual channels of the chip, in which several hundreds of single microchannels are assembled in parallel. A proper methodology is developed accompanying the deep reactive ion etching as well as the anodic bonding, and optimum process conditions necessary for hard and soft micromachining are presented. It has been shown experimentally and theoretically that the silicon-based microchannel leads to increasing streaming potential and higher external current compared to those of the PDMS-based one. A proper comparison between experimental results and theoretical computations allows justification of the validity of our novel devices. It is useful to recognize that a material inducing a higher magnitude of zeta potential has an advantage for obtaining higher power density under the same external resistance.

Journal of the American Chemical Society, 2010

Combined diagnosis and therapy for cancer has been of great interest in medicine. Small interfere... more Combined diagnosis and therapy for cancer has been of great interest in medicine. Small interference RNA (siRNA)-encapsulating polyplexes were covalently coated with small gold nanoparticles (Au NPs) via acid-cleavable linkages in order to explore the possibility of achieving combined stimuli-responsive multimodal optical imaging and stimuli-enhanced gene silencing. In a mildly acidic tumor environment, Au NPs are dissociated from the siRNA-carrying polyplexes, generating various optical signal changes such as diminished scattering intensity, increased variance of Doppler frequency, and blue-shifted UV absorbance (stimuli-responsive imaging). Simultaneously, Au NP dissociation exposes the siRNA-carrying polyplex with elevated surface charge and results in enhanced cellular uptake and transfection (stimuli-enhanced therapy). In this study, the feasibility of achieving combined diagnosis and therapy for cancer (theragnostics) is demonstrated by (1) microscopic and spectrophotometric confirmation of acid-transformation of the nanoparticles, (2) reduced scattering intensity and increased variance of Doppler frequency in an acidic pH upon the nanoparticle's transformation, and (3) simultaneous optical signal changes and gene silencing in vitro under a tumor pH-mimicking condition. This novel type of stimuli-responsive nanotheragnostics will provide a new paradigm for pinpointed, multimodal, and combined imaging and therapy for cancer.

The American Journal of Cardiology, 2015

There have been several reports showing that the statin use is associated with new-onset diabetes... more There have been several reports showing that the statin use is associated with new-onset diabetes mellitus (DM). The aim of the present study was to evaluate the impact of chronic statin use on development of new-onset DM in a series of Asian population. The patients were retrospectively enrolled using the electronic database of Korea University Guro Hospital from January 2004 to February 2010. A total of 10,994 patients without a history of diabetes were analyzed. Baseline lipid profiles, fasting glucose, Hemoglobin (Hb) A1c, and glucose tolerance tests were measured in all patients before statin treatment. Included patients had HbA1c ≤5.7% and fasting glucose level ≤100 (mg/dl). The patients were divided into 2 groups according to the use of statins (the statin group, n = 2,324 patients and the nonstatin group, n = 8,670 patients). To adjust baseline potential confounders, a propensity score-matched analysis was performed using logistic regression model. After propensity score matching, 2 propensity-matched groups (1,699 pairs, n = 3,398, C statistic = 0.859) were generated and analyzed. After propensity score matching, baseline characteristics of both groups were balanced except that the statin group was older and had higher rate of coronary artery disease compared with the nonstatin group. During a 3-year follow-up, the statin group had higher incidence of new-onset DM compared with the nonstatin group (hazard ratio 1.99, 95% CI 1.36 to 2.92, p <0.001), but the statin group showed lower incidence of major adverse cerebral-cardiovascular events compared with the nonstatin group (hazard ratio 0.40, 95% CI 0.19 to 0.85, p <0.001). In the present study, although the use of statins was associated with higher rate of new-onset DM, it markedly improved 3-year cardiovascular outcomes in Asian population.

Advanced Drug Delivery Reviews, 2015

The dynamic and versatile nature of diseases such as cancer has been a pivotal challenge for deve... more The dynamic and versatile nature of diseases such as cancer has been a pivotal challenge for developing efficient and safe therapies. Cancer treatments using a single therapeutic agent often result in limited clinical outcomes due to tumor heterogeneity and drug resistance. Combination therapies using multiple therapeutic modalities can synergistically elevate anti-cancer activity while lowering doses of each agent, hence, reducing side effects. Co-administration of multiple therapeutic agents requires a delivery platform that can normalize pharmacokinetics and pharmacodynamics of the agents, prolong circulation, selectively accumulate, specifically bind to the target, and enable controlled release in target site. Nanomaterials, such as polymeric nanoparticles, gold nanoparticles/cages/shells, and carbon nanomaterials, have the desired properties, and they can mediate therapeutic effects different from those generated by small molecule drugs (e.g., gene therapy, photothermal therapy, photodynamic therapy, and radiotherapy). This review aims to provide an overview of developing multi-modal therapies using nanomaterials ("combo" nanomedicine) along with the rationale, up-to-date progress, further considerations, and the crucial roles of interdisciplinary approaches.

Objectives: This paper aims to explain principles of gist-based health message design and discuss... more Objectives: This paper aims to explain principles of gist-based health message design and discuss their implications for health promotion and public health education. Methods: After reviewing Reyna and Brainerd's Fuzzy Trace Theory(FTT), the authors explicate how to transform FTT into a practical guidance of health message design. Our explication is based upon FTT's reasoning that human intuition, rather than analysis, takes a primary role in message recall and comprehension, followed by judgment and decision making. We expect gist-based message design to be appropriate to serve such intuition. Results: Four principles of gist-based message design are offered: (1) provision of qualitative, as well as quantitative, information of gist, (2) inclusion of visual images corresponding to gist, (3) use of effective message formats to emphasize the gist (4) inclusion of relevant reasons and contextutal information. Conclusions: Gist-based message design has theoretical and practical...

Hyperspectral cameras acquire reflectance values at many different wavelength bands. Dimensions t... more Hyperspectral cameras acquire reflectance values at many different wavelength bands. Dimensions tend to increase because spectral information is stored in each pixel. Several attempts have been made to reduce dimensional problems such as the feature selection using Adaboost and dimension reduction using the Simulated Annealing technique. We propose a novel material detection method that consists of four steps: feature band selection, feature extraction, SVM (Support Vector Machine) learning, and target and specific region detection. It is a combination of the band ratio method and Simulated Annealing algorithm based on detection rate. The experimental results validate the effectiveness of the proposed feature selection and band ratio method.

We proposed a first person shooter for both hands with multiple mouse devices, which are not used... more We proposed a first person shooter for both hands with multiple mouse devices, which are not used in existing games. Players control their movement and shooting separately using dual guns for both hands. For two-hand usage, we designed a display method for multiple mouse pointers. First, we loaded typical physical driver into the memory and registered our developed multiple mouse device driver instead of the existing MS Windows device driver. We then executed both message loop procedures for Windows mouse event handling and those for multiple mouse event handling. We could display multiple mouse cursor images and utilize both mouse devices separately. After that, a prototype game using both hands was developed for an experimental study.

RSC Adv., 2015

ABSTRACT To produce artificial psychological feeling, especially ‘pain’, electrical mimic structu... more ABSTRACT To produce artificial psychological feeling, especially ‘pain’, electrical mimic structure of human skin has been studied. Touch by a sharp and a blunt object induce figurative different deformations of the skin of human fingers. Imitating this phenomenon, the skin mimic device employing the piezoelectric nanowire sensor arrays can generate the electrical ‘pain’ signal with signal processing when a pen cap presses the device. The electrical ‘pain’ signal is expected to enhance the protection mechanism of android robot or mobile phone from harsh environment.

Neuroscience, Jan 4, 2015

Trigeminal ganglia (TG) contain neuronal cell bodies surrounded by satellite glial cells. Althoug... more Trigeminal ganglia (TG) contain neuronal cell bodies surrounded by satellite glial cells. Although peripheral injury is well known to induce changes in gene expression within sensory ganglia, detailed mechanisms whereby peripheral injury leads to gene expression within sensory ganglia are not completely understood. Reactive oxygen species (ROS) are an important modulator of hyperalgesia, but the role of ROS generated within sensory ganglia is unclear. Since ROS are known to affect transcription processes, ROS generated within sensory ganglia could directly influence gene expression and induce cellular changes at the soma level. In this study, we hypothesized that peripheral inflammation leads to cytokine and chemokine production and ROS generation within TG and that transient receptor potential melastatin (TRPM2), a well known oxidative sensor, contributes to ROS-induced gene regulation within TG. The masseter injection of complete Freund's adjuvant (CFA) resulted in a significa...

2012 IEEE International Conference on Automation Science and Engineering (CASE), 2012

ABSTRACT It is important to stably extract horizon lines for sea-based infrared search and track.... more ABSTRACT It is important to stably extract horizon lines for sea-based infrared search and track. Most of the existing solutions for the problems only use single image to detect horizon line. Although this results in good accuracy for some images, it often fails to detect horizons in foggy, occluded environments. In this paper, we propose a novel horizon detection and tracking method that is robust to sensor vibrations and occlusions using image and sensor-based initial horizon detection and robust statistics. Local horizon optimization and tracking produce stable horizons in occluded environments. The experimental results validate the robustness of the proposed method in real infrared images.

Biomater. Sci., 2014

ABSTRACT Development of efficient carriers for small interfering RNA (siRNA) delivery and validat... more ABSTRACT Development of efficient carriers for small interfering RNA (siRNA) delivery and validation tools for assessing in vivo RNA interference (RNAi) efficiency is crucial to advance RNAi-based therapeutics to the clinic. Here, acid-degradable ketalized linear polyethylenimine (KL-PEI) designed for efficient, stimuli-responsive, and biocompatible siRNA delivery was used to complex with GFP-silencing siRNA (GFP siRNA) for in vivo RNAi. The in vivo gene silencing efficiency of GFP siRNA/KL-PEI polyplexes was evaluated at mRNA, protein, and histological levels using a mouse bearing a GFP-expressing tumor. Intravenously injected GFP siRNA/KL-PEI polyplexes significantly reduced GFP expression in tumors and whole blood of mice, depending on the dosage of GFP siRNA and the time course. Average GFP mRNA levels in the tumors of siRNA/KL-PEI polyplex-injected mice were also reduced. The described siRNA carriers and RNAi validation methodologies in this study may provide insightful clues for the development of RNAi-based therapeutics and preclinical trials.

Algorithms and Technologies for Multispectral, Hyperspectral, and Ultraspectral Imagery XIX, 2013

ABSTRACT This paper presents a concealed target detection based on the intersection kernel Suppor... more ABSTRACT This paper presents a concealed target detection based on the intersection kernel Support Vector Machine (SVM). Hyperspectral imagers are widely used in the field of target detection and material analysis. In military applications, it can be used to border protection, concealed target detection, reconnaissance and surveillance. If disguised enemies not detected in advance, the damage of allies will be catastrophic by unexpected attack. Concealed object detection using radar and terahertz method is widely used. However, these active techniques are easily exposed to the enemy. Electronic Optical Counter Counter Measures (EOCCM) using hyperspectral imagers can be a feasible solution. We use the band selected feature directly and the intersection kernel based SVM. Different materials show different spectrums although they look similar in CCD camera. We propose novel concealed target detection method that consist of 4 step, Feature band selection, Feature Extraction, SVM learning and target detection.

Polymer Chemistry, 2012

ABSTRACT Stimuli-triggered degradation and facilitated intracellular release of nucleic acids are... more ABSTRACT Stimuli-triggered degradation and facilitated intracellular release of nucleic acids are key design factors in developing efficient and biocompatible nonviral gene carriers. In this study, a cationic polymer was developed with aims to achieve enhanced gene transfection and low cytotoxicity via rapid biodegradation and subsequent intracellular de-complexation in response to dual stimuli in a cell. Diaminoethane was polymerized to synthesize cationic and hydrolytically degradable poly(amino ester), and then it was further conjugated with acid-degradable amino ketal branches. The resulting polymer, ketalized poly(amino ester) (K-PAE), differentially degrades via rapid hydrolysis of the ketal branches in the mildly acidic endosome and subsequent gradual degradation of the polyester backbone in the cytoplasm. DNA/K-PAE polyplexes underwent acid-triggered de-complexation at an endosomal pH, leading to efficient intracellular release of DNA and significantly enhanced transfection efficiency. In addition, DNA/K-PAE polyplexes demonstrated low cytotoxicity and serum-resistant gene transfection, in comparison with commercial counterpart polymers, promising for efficient and safe gene delivery in vivo. This study presents insightful design clues for developing efficient, versatile, stimuli-responsive, and biocompatible polymers for nonviral gene delivery.

Nanomedicine: Nanotechnology, Biology and Medicine, 2014

Nano-enabled drug delivery (NEDD) systems are rapidly emerging as a key area for nanotechnology a... more Nano-enabled drug delivery (NEDD) systems are rapidly emerging as a key area for nanotechnology application. Understanding the status and developmental prospects of this area around the world is important to determine research priorities, and to evaluate and direct progress. Global research publication and patent databases provide a reservoir of information that can be tapped to provide intelligence for such needs. Here, we present a process to allow for extraction of NEDD-related information from these databases by involving topical experts. This process incorporates in-depth analysis of NEDD literature review papers to identify key subsystems and major topics. We then use these to structure global analysis of NEDD research topical trends and collaborative patterns, inform future innovation directions. This paper describes the process of how to derive nano-enabled drug delivery-related information from global research and patent databases in an effort to perform comprehensive global analysis of research trends and directions, along with collaborative patterns.

Microscopy Research and Technique, 2010

Elucidating dynamic morphological changes of gene-carrying vectors and their nucleic acid release... more Elucidating dynamic morphological changes of gene-carrying vectors and their nucleic acid release under varying intracellular conditions has been a technical challenge. Atomic force microscopy (AFM) was used to observe nucleic acid/polymer polyplexes under endosomal and reducible cytosolic conditions. Both ketalized (acid-degradable) and unmodified (nondegradable) polyethylenimine (PEI) in linear and branched forms were used to prepare plasmid DNA- or siRNA-complexing polyplexes. Then, the polyplexes' complexation and disassembly were observed by in situ AFM in various differentially changing buffers that represent intracellular conditions. Results demonstrated obvious morphological destruction of DNA/ketalized linear PEI (KL-PEI) polyplexes under mildly acidic endosomal conditions, whereas no morphological changes were observed by DNA/ketalized branched PEI (KB-PEI) under the same conditions. In addition, siRNA was more efficiently dissociated from KL-PEI than KB-PEI under the same conditions. Nondegradable PEI did not show any evidence that DNA or siRNA was released. Anionic biomacromolecules (e.g., heparan sulfate), which was hypothesized to dissociate nucleic acids from cationic polymers, did not successfully disassemble polyplexes but appeared to be adsorbed on cationic polymers. The in situ AFM results combined with in vitro cellular transfection and gene silencing indicated that efficient endosomal escape of plasmid DNA in a compact polyplex form is required for efficient gene expression. On the contrary, rapid dissociation of siRNA from its cationic carrier is crucial for efficient gene silencing. The findings of this study may provide new insightful information for designing stimuli-responsive nonviral gene vectors as well as expanding tools for investigating nonviral vectors in nanoscales under biologically inspired conditions.

Lab on a Chip, 2006

To elaborate on the applicability of the electrokinetic micro power generation, we designed and f... more To elaborate on the applicability of the electrokinetic micro power generation, we designed and fabricated the silicon-glass as well as the PDMS-glass microfluidic chips with the unique features of a multi-channel. Besides miniaturizing the device, the key advantage of our microfluidic chip utilization lies in the reduction in water flow rate. Both a distributor and a collector taking the tapered duct geometry are positioned aiming the uniform distribution of water flow into all individual channels of the chip, in which several hundreds of single microchannels are assembled in parallel. A proper methodology is developed accompanying the deep reactive ion etching as well as the anodic bonding, and optimum process conditions necessary for hard and soft micromachining are presented. It has been shown experimentally and theoretically that the silicon-based microchannel leads to increasing streaming potential and higher external current compared to those of the PDMS-based one. A proper comparison between experimental results and theoretical computations allows justification of the validity of our novel devices. It is useful to recognize that a material inducing a higher magnitude of zeta potential has an advantage for obtaining higher power density under the same external resistance.

Journal of the American Chemical Society, 2010

Combined diagnosis and therapy for cancer has been of great interest in medicine. Small interfere... more Combined diagnosis and therapy for cancer has been of great interest in medicine. Small interference RNA (siRNA)-encapsulating polyplexes were covalently coated with small gold nanoparticles (Au NPs) via acid-cleavable linkages in order to explore the possibility of achieving combined stimuli-responsive multimodal optical imaging and stimuli-enhanced gene silencing. In a mildly acidic tumor environment, Au NPs are dissociated from the siRNA-carrying polyplexes, generating various optical signal changes such as diminished scattering intensity, increased variance of Doppler frequency, and blue-shifted UV absorbance (stimuli-responsive imaging). Simultaneously, Au NP dissociation exposes the siRNA-carrying polyplex with elevated surface charge and results in enhanced cellular uptake and transfection (stimuli-enhanced therapy). In this study, the feasibility of achieving combined diagnosis and therapy for cancer (theragnostics) is demonstrated by (1) microscopic and spectrophotometric confirmation of acid-transformation of the nanoparticles, (2) reduced scattering intensity and increased variance of Doppler frequency in an acidic pH upon the nanoparticle's transformation, and (3) simultaneous optical signal changes and gene silencing in vitro under a tumor pH-mimicking condition. This novel type of stimuli-responsive nanotheragnostics will provide a new paradigm for pinpointed, multimodal, and combined imaging and therapy for cancer.

Journal of Controlled Release, 2009

To maximize therapeutic effects, targeted delivery of nucleic acids (e.g., DNA and RNA) in their ... more To maximize therapeutic effects, targeted delivery of nucleic acids (e.g., DNA and RNA) in their appropriate intracellular targets is highly desirable. In this study, primary amines of a model polymeric nonviral carrier, polyethylenimine (PEI), at two molecular weights (0.8 and 25 kDa) were differentially ketalized (i.e., 17-96%) in order to explore the possibility of precisely modulating intracellular localization of plasmid DNA-and siRNA-containing polyplexes. The size of the polyplexes revealed that the ketalization ratios of 35 to 70% were found to be the most efficient in condensing nucleic acids with the ketalized low molecular weight PEI (LMW PEI), while high molecular weight PEI (HMW PEI) ketalized at the ratio of 23% condensed nucleic acids most efficiently. Ketalization of LMW PEI (up to 70%) enhanced transfection; however, ketalization of HMW PEI reduced its transfection capability. On the contrary, HMW PEI ketalized at 23 and 37% ratios showed significant RNA interference, while LMW PEI could not successfully inhibit gene expression regardless of ketalization ratios. The results were explained by confocal microscopic studies demonstrating that ketalization ratios, molecular weights of ketalized PEI, and types of nucleic acids complexed in the polyplexes play crucial roles in intracellular localization of nucleic acids/ketalized PEI polyplexes and affect DNA transfection and RNA interference efficiencies. All ketalized PEI showed negligible cytotoxicity. This study implies a feasibility of selectively localizing nucleic acids in their intracellular targets by employing differentially tailored polymeric gene carriers.