Photothermally enhanced photodynamic therapy based on glutathione-responsive pheophorbide a-conjugated gold nanorod formulations for cancer theranostic applications

Jongseon Choi,So Yeon Kim 한국공업화학회 2020 Journal of Industrial and Engineering Chemistry Vol.85 No.-

Nanocarriers have provided a new platform for the selective delivery of therapeutic agents into targetedcells and tissues using safe, efficient, and tractable routes. In particular, the integration of multipletherapeutic/diagnostic modalities into a single system has the great potential of enhancing theranosticefficiency against serious diseases with reduced side effects. In this study, a new light-triggeredtheranostic system using photosensitizer-conjugated gold nanorods (AuNR) with glutathione (GSH)-sensitive linkages was developed for cancer imaging and combinational phototherapy of photodynamictherapy (PDT) and photothermal therapy (PTT) to achieve a synergistic cancer treatment. AuNRs withvarious aspect ratios were prepared as photothermal agents, and then a folic acid (FA)-PEG blockcopolymer (FAP) and pheophorbide a (Pheo) were chemically conjugated to the surface of AuNRs foractive tumor targeting and PDT, respectively. The configuration of Pheo-conjugated AuNR nanocarriershas been precisely controlled through adjusting the feed composition ratio and the relationship betweenaspect ratio and absorption band of AuNRs. In particular, an AuNR with an aspect ratio of 3.84 andlongitudinal plasmon resonance at 873 nm (Pheo-conjugated AuNR100) exhibited superior performancein singlet oxygen generation, photothermal conversion effect, and GSH-mediated selective release ofPheo. Moreover, it also showed tumor targeting activity and a PDT-PTT synergistic effect. These resultsindicate that this multifunctional AuNR system with tumor targeting ability and GSH-sensitive linkageswould be highly efficient for noninvasive cancer treatment by integrating cancer imaging diagnostics andsynergistic therapy.

Photothermally enhanced photodynamic therapy based on glutathione-responsive pheophorbide <i>a</i>-conjugated gold nanorod formulations for cancer theranostic applications

Choi, Jongseon,Kim, So Yeon Elsevier 2020 Journal of industrial and engineering chemistry Vol.85 No.-

<P><B>Abstract</B></P> <P>Nanocarriers have provided a new platform for the selective delivery of therapeutic agents into targeted cells and tissues using safe, efficient, and tractable routes. In particular, the integration of multiple therapeutic/diagnostic modalities into a single system has the great potential of enhancing theranostic efficiency against serious diseases with reduced side effects. In this study, a new light-triggered theranostic system using photosensitizer-conjugated gold nanorods (AuNR) with glutathione (GSH)-sensitive linkages was developed for cancer imaging and combinational phototherapy of photodynamic therapy (PDT) and photothermal therapy (PTT) to achieve a synergistic cancer treatment. AuNRs with various aspect ratios were prepared as photothermal agents, and then a folic acid (FA)-PEG block copolymer (FAP) and pheophorbide <I>a</I> (Pheo) were chemically conjugated to the surface of AuNRs for active tumor targeting and PDT, respectively. The configuration of Pheo-conjugated AuNR nanocarriers has been precisely controlled through adjusting the feed composition ratio and the relationship between aspect ratio and absorption band of AuNRs. In particular, an AuNR with an aspect ratio of 3.84 and longitudinal plasmon resonance at 873nm (Pheo-conjugated AuNR100) exhibited superior performance in singlet oxygen generation, photothermal conversion effect, and GSH-mediated selective release of Pheo. Moreover, it also showed tumor targeting activity and a PDT-PTT synergistic effect. These results indicate that this multifunctional AuNR system with tumor targeting ability and GSH-sensitive linkages would be highly efficient for noninvasive cancer treatment by integrating cancer imaging diagnostics and synergistic therapy.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

광역학적/광열치료 응용을 위한 광증감제가 결합한 골드 나노로드의 합성 및 특성분석

최종선 ( Jongseon Choi ),김소연 ( So Yeon Kim ) 한국공업화학회 2016 공업화학 Vol.27 No.6

최근 효과적인 암 치료 방법으로 광역학치료(photodynamic therapy)와 광열치료(photothermal therapy)가 주목받고 있다. 본 연구에서는 광열치료에 필요한 광열인자로써의 역할을 할 수 있는 골드 나노로드(AuNR)를 합성하고, 그 표면에 광역학 치료를 위한 광증감제(photosensitizer)를 결합하였다. 즉, 골드 나노로드를 체내에 오래 머무르도록 하기 위해 PEG(polyethylene glycol) 및 효과적인 암 표적지향성을 위해 FA (folic acid) 리간드를 도입하였고, FA-PEG와 poly-β-benzyl-L-aspartate (PBLA)로 이루어진 블록 공중합체를 3,4-dihydroxy hydrocinnamic acid (HCA) linker를 사용하여 골드나노로드의 표면개질을 하였다. 또한 AgNO₃의 feeding ratio 변화를 통해 다양한 aspect ratio를 갖는 골드 나노로드를 합성하였고, UV-visible spectrophotometer, ¹H-NMR, XPS, TEM 분석을 통해 FA-PEG-P(Asp)₅₀-HCA-AuNR100의 물리 화학적 특성과 morphology를 분석하였고, 성공적인 표면 개질을 확인할 수 있었다. 골드 나노로드의 표면 개질을 통한 생체 적합성 약물전달체의 합성은 효과적인 암 진단 및 다양한 광역학/광열치료 분야에 응용이 될 수 있을 것으로 기대된다. Recently, photodynamic and photothermal therapies have received increasing attention as an effective cancer treatment. In this study, a gold nanorod (AuNR) colloidal solution was synthesized as a hyperthermia agent for photothermal therapy and also modified with photosensitizer (PS) for photodynamic therapy. PEG (polyethylene glycol) and FA (folic acid) ligand were also introduced into AuNR for the long circulation in human body and efficient targeting of cancer cells, respectively and AuNRs were modified with FA-PEG and poly-β-benzyl-L-aspartate (PBLA) block copolymers through a 3,4-dihydroxy hydro-cinnamic acid (HCA) linker. A series of AuNRs with various aspect ratios were synthesized by controlling the feeding ratio of AgNO₃. The physicochemical property and morphology of synthesized AuNR100 and FA-PEG-P(Asp)₅₀-HCA-AuNR100 were analyzed by UV-visible spectrophotometer, ¹H NMR, XPS measurements, TEM. The surface modified AuNR carrier with biocompatibility could be applied for the effective diagnosis as well tumor phototherapy.

아크릴계 단량체 2-HEA와 EGPA의 조성에 따른 고분자 분산형 액정(PDLC)의 전기광학적 특성 평가

최종선 ( Jongseon Choi ),김영대 ( Young Dae Kim ),김소연 ( So Yeon Kim ) 한국공업화학회 2019 공업화학 Vol.30 No.2

지난 수십 년 동안 고분자 분산형 액정(polymer dispersed liquid crystal, PDLC)은 전기광학적으로 전환이 가능한 특성으로 인해 빛의 투과도를 자유롭게 조절할 수 있는 smart window를 개발하는 물질로서 주목을 받아왔다. 본 연구에서는 높은 구동전압과 낮은 명암비 등의 PDLC 문제점을 해결하기 위해 아크릴계 단량체 2-hydroxyethyl acrylate (2-HEA)와 ethylene glycol phenyl ether acrylate (EGPA)의 조성이 PDLC의 전기광학 특성에 미치는 영향을 평가하였다. 상온에서 10 cps 이하의 낮은 점도를 나타내는 2-HEA와 EGPA 단량체를 사용하여 제조하는 경우 보다 쉽게 capillary action에 의해서 indium tin oxide (ITO) glass 사이에 주입하는 공정이 가능하였다. Phenyl group를 포함한 EGPA 단량체가 대부분으로 이루어진 1 : 9인 단량체 혼합물로 만들어진 PDLC cell의 경우 전기장을 인가하지 않은 경우에도 불투명한 상태가 관측되지 않았고 인가 전압에 따라 매우 불안정한 투과율을 나타내었다. Cell gap thickness가 증가함에 따라 문턱전압(threshold voltage, V_th)과 포화전압(saturation voltage, V_sat)도 증가하는 경향을 나타내었으며, 20 μm의 cell gap thickness를 갖는 PDLC cell이 10과 40 μm의 경우 보다 상대적으로 높은 명암비를 나타내었다. 특히, 7 : 3 비율의 2-HEA : EGPA 단량체 혼합물을 사용하여 제조된 PDLC cell의 경우가 낮은 구동전압과 높은 명암비의 가장 우수한 전기광학적 특성을 나타내었다. Over the past several decades, the polymer dispersed liquid crystal (PDLC) has received particular attention as a material for developing smart window due to their electro-optical switchable properties. In this study, PDLC cells were fabricated using acrylate monomers, namely 2-hydroxyethyl acrylate (2-HEA) and ethylene glycol phenyl ether acrylate (EGPA), and the effect of the monomer composition on their electro-optical properties was investigated. The monomer mixture with a low viscosity (~10 cps) was easily filled between indium tin oxide (ITO) glasses by capillary action at room temperature. PDLC cells prepared using the mixture ratio of 1 : 9 (2-HEA : EGPA) did not show a complete opaque state at a 0 V condition but exhibited unstable electro-optical properties under an electric field. As the LC composition increased in the reaction mixture for PDLC cell preparation, the V_th (threshold voltage) and V_sat (saturation voltage) values as well as contrast ratio (CR) increased. V_th and V_sat values also increased with the cell gap thickness. PDLC cells with a 20 μm cell gap thickness exhibited higher CR than those with 10 and 40 μm cell gap thicknesses. Particularly, PDLC cells prepared using the mixture ratio of 7 : 3 (2-HEA : EGPA) showed excellent electro-optical properties such as a low driving voltage and high contrast ratio.

히트펌프 기반 통합형 냉난방-환기 시스템 성능 평가에 관한 실험적 연구

최종선(Jongseon Choi),이홍철(Hongcheol Lee),황인주(Inju Hwang) 대한기계학회 2011 대한기계학회 춘추학술대회 Vol.2011 No.5

본 연구에서는 제로카본 그린홈 적용을 위한 대기열원 히트펌프 기반 IHVAC 시스템 제시를 목적으로 IHVAC 구성 유닛의 최적 조합 및 운전조건을 도출하고자 하였다. IHVAC 최적 시스템의 제시를 위하여 IHVAC 패키지의 구성 형태, 운전 조건에 따라 에너지의 성능을 검토하였다. 이를 위하여 3가지 형태의 IHVAC 패키지의 운전 성능을 운전 조건에 따라 KS C 9306에 기준하여 비교 평가하였다. IHVAC 패키지는 구성 형태와 운전 조건에 띠라 전열 교환 성능과 현열 열 교환 성능이 상호 보완적이었으며, 70-90% 범위의 온도교환 효율과 3.0~4.0 범위의 COP 성능을 나타내었다. 이를 바탕으로 제로카본 그린홈 실증주택 작용을 위한 IHVAC 패키지(안)를 제시하였다. In this paper, IHVAC system base on an air to air heat pump is proposed for HVAC package of zero carbon green home, 3 types of the IHVAC package are compared by variable operating conditions to review energy performance of the system. It was experimented by the KS C 9306. The results of the experiment with enthalpy heat exchanger and sensible heat exchanger were shown temperature effectiveness of 70~80% and COP oas 3.0~4.0 by controlling type. Through this study, IHVAC system of the type 2-2 is proposed for zero carbon green home.

Measurement of Mechanical Properties according to the Thickness of Anodic Aluminum Oxide through Nanoindentation Test

최종선(Jongseon Choi),황현도(Hyundo Hwang),정종현(Jonghyeon Jeong),황운봉(Woonbong Hwang) Korean Society for Precision Engineering 2021 한국정밀공학회지 Vol.38 No.3

Fabrication of 4 × 1 signal combiner for high-power lasers using hydrofluoric acid

Choi, In Seok,Park, Jongseon,Jeong, Hoon,Kim, Ji Won,Jeon, Min Yong,Seo, Hong-Seok The Optical Society 2018 Optics express Vol.26 No.23

Fibroblasts Enhance the In Vitro Survival of Human Memory and Na?ve B Cells by Maintaining Intracellular Levels of Glutathione

Jongseon Choe,Euh Jun Jeong,In Yong Lee,Jin-Suk Choi,In Su Cheon,Gu Kang 한국분자세포생물학회 2004 Molecules and cells Vol.17 No.3

TNF-α elicits phenotypic and functional alterations of vascular smooth muscle cells by miR-155-5p–dependent down-regulation of cGMP-dependent kinase 1

Choi, Seunghwan,Park, Minsik,Kim, Joohwan,Park, Wonjin,Kim, Suji,Lee, Dong-Keon,Hwang, Jong Yun,Choe, Jongseon,Won, Moo-Ho,Ryoo, Sungwoo,Ha, Kwon-Soo,Kwon, Young-Guen,Kim, Young-Myeong American Society for Biochemistry and Molecular Bi 2018 The Journal of biological chemistry Vol.293 No.38

<P>cGMP-dependent protein kinase 1 (PKG1) plays an important role in nitric oxide (NO)/cGMP-mediated maintenance of vascular smooth muscle cell (VSMC) phenotype and vasorelaxation. Inflammatory cytokines, including tumor necrosis factor-alpha(TNF alpha), have long been understood to mediate several inflammatory vascular diseases. However, the underlying mechanism of TNF alpha-dependent inflammatory vascular disease is unclear. Here, we found that TNF alpha treatment decreased PKG1 expression in cultured VSMCs, which correlated with NF-kappa B-dependent biogenesis of miR-155-5p that targeted the 3'-UTR of PKG1 mRNA. TNF alpha induced VSMC phenotypic switching from a contractile to a synthetic state through the down-regulation of VSMC marker genes, suppression of actin polymerization, alteration of cell morphology, and elevation of cell proliferation and migration. All of these events were blocked by treatment with an inhibitor of miR-155-5p or PKG1, whereas transfection with miR-155-5p mimic or PKG1 siRNA promoted phenotypic modulation, similar to the response to TNF alpha. In addition, TNF alpha-induced miR-155-5p inhibited the vasorelaxant response of de-endothelialized mouse aortic vessels to 8-Br-cGMP by suppressing phosphorylation of myosin phosphatase and myosin light chain, both of which are downstream signal modulators of PKG1. Moreover, TNF alpha-induced VSMC phenotypic alteration and vasodilatory dysfunction were blocked by NF-kappa B inhibition. These results suggest that TNF alpha impairs NO/cGMP-mediated maintenance of the VSMC contractile phenotype and vascular relaxation by down-regulating PKG1 through NF-kappa B-dependent biogenesis of miR-155-5p. Thus, the NF-kappa B/miR-155-5p/PKG1 axis may be crucial in the pathogenesis of inflammatory vascular diseases, such as atherosclerotic intimal hyperplasia and preeclamptic hypertension.</P>

Development of an Estimation Instrument of Acoustic Lens Properties for Medical Ultrasound Transducers

Choi, Hojong,Jeong, Jongseon Johnson,Kim, Jungsuk Hindawi 2017 Journal of healthcare engineering Vol.2017 No.-

<P>In medical ultrasound transducers, the transmission mode (pass-through) approach has been used to estimate the characteristics of the acoustic lens. However, it is difficult to measure the acoustic lens properties with high precision because of human, systemic, or mechanical measurement errors. In this paper, we propose a low-cost estimation instrument for acoustic lens properties connected with a customized database. In the instrument, three-axis and one-axis transmitting and material fixtures accurately align the transmitting and receiving transducers separately. Through the developed instrument, we obtained a precise standard deviation of the attenuation coefficient and velocity of the acoustic lens material of 0.05 dB/cm and 2.62 m/s, respectively. Additionally, the simultaneous alignment between the fixtures is controllable with developed programs, thus generating very accurate information of the acoustic lens about the testing ultrasound transducer. In our instrument, the database could support users in managing the result data efficiently. User programs developed using LabVIEW provide the capability to obtain precise values of the attenuation coefficient and velocity, which represent the fundamental material characteristics of the acoustic lens of the medical ultrasound transducers. The developed review program of the customized database can also search the acoustic lens information and store the experimental results.</P>