Yongdoo Choi - Academia.edu (original) (raw)

Papers by Yongdoo Choi

Proceedings of the 2nd World Congress on New Technologies, 2016

Journal of Pharmaceutical Investigation, 2018

International Journal of Pharmaceutics, 2001

Journal of Biomaterials Science, Polymer Edition, 2001

The aggregation of poly(®-hydroxy acid) microspheres during ethylene oxide (EO) gas sterilization... more The aggregation of poly(®-hydroxy acid) microspheres during ethylene oxide (EO) gas sterilization makes it dif cult for the microspheres to be used in clinical applications. In this study, six kinds of PLLA-PEG-PLLA triblock copolymers (TriPLE) were synthesized with various composition ratios of PEG / PLLA in the range of 0.012 to 0.103. TriPLE microspheres were prepared by the oil-in-water emulsion method. TriPLE microspheres were characterized by using 1 H-NMR, gel permeation chromatography (GPC), and differential scanning calorimetry (DSC). After sterilization by EO gas at 55 ± C, the microspheres were analyzed by scanning electron microscope (SEM), laser diffractometry, standard sieves, X-ray diffraction (XRD), GPC, and DSC. When the composition ratio of PEG / PLLA was above 0.02, the initial crystallinity of TriPLE in microspheres was as high as 50%, and the microspheres were suitable to be sterilized by EO gas. On the other hand, TriPLE microspheres, which had composition ratios of PEG / PLLA below 0.02, had low initial crystallinities of about 30%, and aggregated during EO gas sterilization. For these microspheres, crystallinity increased up to 50% during the sterilization, whereas other TriPLE microspheres did not show any changes in crystallinity. Therefore, the aggregation of TriPLE microspheres during EO gas sterilization was markedly reduced as the initial crystallinity of TriPLE in the microspheres was increased.

Journal of Biomaterials Science, Polymer Edition, 2002

Drug Development Research, 2004

All‐trans retinoic acid (atRA)‐loaded microspheres severely induce inflammatory responses after m... more All‐trans retinoic acid (atRA)‐loaded microspheres severely induce inflammatory responses after microsphere implantation. Fibroblasts and a thick band of fibrous capsule resulting from the inflammatory responses could hamper drug permeation to the bloodstream because fibroblasts actively metabolize atRA into polar metabolites and the thick fibrous capsule acts as a diffusion barrier. In the present study, we investigated whether the fibroblast proliferation and collagen deposition induced by atRA released from microspheres might affect the atRA concentration in plasma and atRA metabolism with or without treatment of dexamethasone as an anti‐inflammatory drug. After subcutaneous injection of atRA‐loaded microspheres in rats, it was observed that atRA‐loaded microspheres induced severe inflammatory responses and stimulated fibroblast proliferation and collagen deposition in fibrous capsules. On the other hand, the orally treated dexamethasone effectively prevented inflammatory respons...

Drug Development Research, 2002

Previously, poly(L‐lactide) microspheres containing retinoic acid (RA) had been prepared for pare... more Previously, poly(L‐lactide) microspheres containing retinoic acid (RA) had been prepared for parenteral administration in order to overcome “acute retinoic acid resistance.” In this study, acute toxicities of RA‐loaded microspheres were investigated in mice after the microspheres were injected intramuscularly. The maximum dose of RA in the microspheres was determined by considering both the injection volume and dispersion of microspheres in the vehicle media, and the dose levels were determined to be 0, 90, 180, and 360 mg RA/kg. Mice were carefully observed for any clinical signs for 14 days, and gross observation of the organs was performed at 14 days. When a dose of 90 mg RA/kg was administered, no severe toxicities were observed; however, with the administration of 180 and 360 mg RA/kg, abnormal appearances of organs, such as discolor, atrophy, hemorrhage, etc., were observed. There were no mortalities or bone fractures observed at any of the doses. In our previous study of canc...

Drug Development Research, 2003

Biodegradable microspheres containing all‐trans‐retinoic acid (atRA) were prepared previously to ... more Biodegradable microspheres containing all‐trans‐retinoic acid (atRA) were prepared previously to enhance the clinical efficacy of atRA for chemoprevention. In this study, subacute toxicity of atRA in sustained release was evaluated after subcutaneous administration of 0, 25, 50, and 100 mg atRA/kg of atRA‐loaded microspheres. After the subcutaneous injection of atRA‐loaded microspheres, the atRA concentration in plasma was maintained in the range of 3.5–25 ng/ml for 2–3 weeks. When 100 mg atRA/kg was administered, the atRA concentration in plasma was maintained at levels greater than 10 ng/ml and severe toxic effects were observed. When the dose of 50 mg atRA/kg was administered, the plasma concentration of atRA was maintained below 10 ng/ml over 3 weeks and only mild signs of toxicity were observed. Therefore, it was concluded that the dosage of atRA‐loaded microspheres should be less than 50 mg atRA/kg for chemopreventive applications against carcinogenesis. Considering recovery f...

Chem. Commun., 2014

A folate receptor-specific activatable probe for in vivo near-infrared fluorescence imaging with ... more A folate receptor-specific activatable probe for in vivo near-infrared fluorescence imaging with a high target-to-background ratio was synthesized.

Carbohydrate Polymers, Feb 1, 2013

The present study was performed to investigate the stability of W/O/W emulsions containing 4-␣glu... more The present study was performed to investigate the stability of W/O/W emulsions containing 4-␣glucanotransferase (4␣GTase)-treated starch against environmental stresses such as heating, shearing, and repeated freeze-thawing. W/O/W emulsions were subjected to thermal processing at different temperatures ranging from 30 to 90 • C for 30 min, constant shear for 0-7 min, and freeze-thaw cycling between −20 • C and 30 • C, respectively, and followed by encapsulation efficiency (EE) measurement. As for the case of thermal stress, it was clearly shown that addition of 4␣GTase-treated starch in the internal aqueous phase of emulsions helped to maintain higher EE during thermal processing. However, at lower PGPR level (2%), the addition of 4␣GTase-treated starch dramatically reduced EE at temperatures higher than 70 • C, which was probably related to the melting of 4␣GTase-treated starch gel. The incorporation of 4␣GTase-treated starch improved the stability of emulsions during shearing process, but could not prevent W/O/W emulsions from creaming and destabilizing during freeze-thaw cycling.

Cancers

Background: Prediction of resistance mechanisms for epidermal growth factor receptor-tyrosine kin... more Background: Prediction of resistance mechanisms for epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) remains challenging. Thus, we investigated whether resistant cancer cells that expand shortly after EGFR-TKI treatment would eventually cause the resistant phenotype. Methods: We generated two EGFR-mutant lung cancer cell lines resistant to gefitinib (PC9GR and HCC827GR). The parent cell lines were exposed to short-term treatment with gefitinib or paclitaxel and then were assessed for EGFR T790M mutation and C-MET expression. These experiments were repeated in vivo and in clinically relevant patient-derived cell (PDC) models. For validation in clinical cases, we measured these gene alterations in plasma circulating tumor DNA (ctDNA) before and 8 weeks after starting EGFR-TKIs in four patients with EGFR-mutant lung cancer. Results: T790M mutation was only detected in the PC9GR cells, whereas C-MET amplification was detected in the HCC827GR cells. The T790M mutat...

Sensors

We developed a single-camera-based near-infrared (NIR) fluorescence imaging device using indocyan... more We developed a single-camera-based near-infrared (NIR) fluorescence imaging device using indocyanine green (ICG) NIR fluorescence contrast agents for image-induced surgery. In general, a fluorescent imaging system that simultaneously provides color and NIR images uses two cameras, which is disadvantageous because it increases the imaging head of the system. Recently, a single-camera-based NIR optical imaging device with quantum efficiency partially extended to the NIR region was developed to overcome this drawback. The system used RGB_NIR filters for camera sensors to provide color and NIR images simultaneously; however, the sensitivity and resolution of the infrared images are reduced by 1/4, and the exposure time and gain cannot be set individually when acquiring color and NIR images. Thus, to overcome these shortcomings, this study developed a compact fluorescent imaging system that uses a single camera with two complementary metal–oxide semiconductor (CMOS) image sensors. Sensit...

Materials and methods Materials Pyrrole (98 %), polyvinylpyrrolidone (PVP, MW ~29,000), and iron(... more Materials and methods Materials Pyrrole (98 %), polyvinylpyrrolidone (PVP, MW ~29,000), and iron(III) chloride hexahydrate (FeCl 3 •6H 2 O), trypsin from porcine pancreas (13,100 U/mg), and hyaluronidase (1,228 U/mg) were purchased from Sigma-Aldrich (St. Louis, MO, USA). Hyaluronic acid (HA, Mw 39,000 Da) was obtained from Lifecore Biomedical (Chaska, MN, USA) and used as received. Chlorin e4 (Ce4) was purchased from Frontier Scientific, Inc. (Logan, UT, USA). Singlet oxygen sensor green (SOSG), which is an agent for detecting singlet oxygens, was obtained from Invitrogen Corp. (Carlsbad, CA, USA). Methods Synthesis and characterization of positively charged-Ce4 (PCe4) Positively charged photosensitizer (PCe4) was prepared by conjugating Ce4 with RRK peptide. Briefly, the peptide (RRK) was synthesized using a standard solid-phase peptide synthesis protocol. Coupling was carried out using Fmoc amino acid (8 eq), Nhydroxybenzotriazole (HOBt, 8 eq), N,N-diisopropylethylamine (DIPEA,16 eq) in DMF for 2 h. After each step, resin washing was performed using DMF and methanol 2 times each. The Fmoc protecting group was removed by rocking in 20% piperidine in DMF for 10 min (twice). Ce4 and HOBt/DIPEA in DMF were added to the peptide-attached resin. The mixture was reacted for 12 h and suctioned, and then the resin was washed with DMF, MeOH, and DMF. When the reaction was completed, crude peptide was cleaved from the resin using a mixture of TFA/EDT/thioanisole/TIS/deionized water (90/2.5/2.5/2.5/2.5 volume) for 2 h. The solution was precipitated with cold ether and pelleted using a centrifuge. The solid was collected and air-dried. Crude peptide was dissolved in deionized water and purified by prep-LC, lyophilized, and preserved in a refrigerator before use. The molecular weights of PCe4 were measured using LC/MSD

Quantitative Imaging in Medicine and Surgery, 2020

Background: Accurate identification of tumor sites and boundaries is of paramount importance duri... more Background: Accurate identification of tumor sites and boundaries is of paramount importance during minimally invasive surgery. Although laparoscopic resection is being increasingly and widely performed for early gastric and colorectal cancers, the detection of tumors located inside the stomach and intestine is difficult owing to the lack of tactile sensation. Here, we propose the application of an indocyanine green (ICG)-loaded alginate hydrogel system as a fluorescence surgical marker for precise laparoscopic operations. Methods: A physical complex of ICG and human serum albumin (HSA) was mixed with sodium alginate to form an injectable hydrogel system. Calcium carbonate and D-gluconic acid (GA) were added to the gel to control its strength and gelation time, respectively. The optimal conditions for the preparation of injectable hydrogels were determined by analyzing the fluorescence spectra and sol-gel transition time of the prepared samples at various concentrations and compositions. Next, the aqueous solutions of ICG, ICG-HSA, and ICG-HSA-loaded alginate were subcutaneously injected into nude mice (three mice per group), and nearinfrared (NIR) fluorescence images of the mice (λ ex. =780 nm, λ em. =845 nm) were obtained at different points in time for 8 days. Then, fluorescence intensities at the injection sites, target-to-background ratio, and areas of ICG fluorescence were analyzed. Finally, the potential utility of ICG-HSA-loaded alginate hydrogel as a surgical marker was evaluated in a porcine model. The ICG-HSA-loaded alginate solution was injected into three sites in the submucosal space of the porcine stomach via a catheter. A fluorescent laparoscopic system was installed on the abdomen of the pig 3 days post-injection, and the fluorescence signal generated from the fluorescence surgical marker located inside the stomach was evaluated using the fluorescence laparoscope system (λ ex. =785 nm, λ em. =805 nm). Results: The optimal concentration of ICG-HSA complex was determined to be 30 μM, and maximum fluorescence intensity of the complex was obtained at a 1:1 mole ratio of HSA to ICG. The subcutaneous injection of ICG or ICG-HSA solution in mice resulted in the rapid spread of the fluorescence signal around the injection site in 3 h, and a weak fluorescence was detected at the injection site 24 h post-injection. In contrast, the fluorescence detection time was effectively prolonged up to 96 h post-injection in the case of ICG-HSA-loaded alginate gel, while diffusion of the injected ICG from the injection site was effectively prevented. In the laparoscopic operation, injection sites of the hydrogel in porcine stomach could be accurately detected in real time even after 3 days. Conclusions: This alginate hydrogel system may be potentially useful as an effective surgical marker in terms of accuracy and persistence for laparoscopic operation.

Frontiers in Chemistry, 2017

In this study, we synthesized manganese dioxide nanoparticles (MnO 2 NPs) stabilized with biocomp... more In this study, we synthesized manganese dioxide nanoparticles (MnO 2 NPs) stabilized with biocompatible polymers (polyvinylpyrrolidone and polyacrylic acid) and analyzed their effect on non-small cell lung cancer (NSCLC) cells with or without gefitinib resistance in vitro. MnO 2 NPs showed glutathione (GSH)-responsive dissolution and subsequent enhancement in magnetic resonance (MR) imaging. Of note, treatment with MnO 2 NPs induced significant cytotoxic effects on NSCLC cells, and additional dose-dependent therapeutic effects were obtained upon X-ray irradiation. Normal cells treated with MnO 2 NPs were viable at the tested concentrations. In addition, increased therapeutic efficacy could be achieved when the cells were treated with MnO 2 NPs in hypoxic conditions. Therefore, we conclude that the use of MnO 2 NPs in MR imaging and combination radiotherapy may be an efficient strategy for the imaging and therapy of NSCLC.

Scientific Reports, 2017

Gastric cancer is the third most common cause of cancer mortality, and the survival rate of stage... more Gastric cancer is the third most common cause of cancer mortality, and the survival rate of stage IV advanced gastric cancer (AGC) patients with distant metastasis is very low. Thus, the detection and eradication of disseminated cancer cells by targeting cell surface molecules in AGC would improve patient survival. The hyaluronic acid receptor, CD44, has various isoforms generated by alternative splicing, and some isoforms are known to be correlated to gastric cancer. In this study, to find out the most appropriate CD44v for targeting AGC, we analysed the expression differences of CD44 isoforms at the mRNA level in stomach cancer cell lines as well as in 74 patients with AGC by using exon-specific qRT-PCR. Among the CD44v isoforms, CD44v8-10 was determined as the most promising biomarker for the development of theranostic agents of gastric cancer. Next, we synthesised the conjugate of anti-CD44v9 antibody with near-infrared fluorophore or photosensitiser, and then demonstrated its f...