Development of versatile platforms for constructing near-infrared photosensitizer based theragnosis system = 근적외선 형광체를 기반으로 한 새로운 테라그노시스 플랫폼 개발
서명 / 저자 Development of versatile platforms for constructing near-infrared photosensitizer based theragnosis system = 근적외선 형광체를 기반으로 한 새로운 테라그노시스 플랫폼 개발 / Ilkoo Noh.
저자명 Noh, Ilkoo ; 노일구
발행사항 [대전 : 한국과학기술원, 2019].
Online Access 비공개원문





학술문화관(도서관)2층 패컬티라운지(학위논문)

DCBE 19031

SMS전송 소장위치






Theragnosis (therapy + diagnosis) is notable for early detection in the treatment of cancers, thereby increasing the survival rate of patients by enhancing the therapeutic effect. Currently, organic and inorganic materials have been studied with these theragnosis tools, and fluorescence, PET, CT, and PA have been used as methods for in vivo diagnosis of abnormal sites. Among these tools, organic systems can overcome the problems of toxicity and bioavailability of inorganic systems, and many studies have been conducted. In particular, an organic photosensitizer having a near-infrared light absorber has excellent resolution and contrast index compared to those of the conventional visible light region. The ability of these photosensitizers also includes a phototherapy property (such as for photodynamic therapy and photo-thermal therapy) by which is possible to deliver local therapy depending on irradiation by a particular laser. Therefore, I have developed an organic system with various properties, which enables diagnosis due to its high resolution and delivers laser phototherapy at the diagnosed position. In the work reported in this thesis, I constructed a near-infrared cyanine dye-based theragnosis system from two directions. First, a single-molecule photosensitizer capable of targeting cancer mitochondria was designed to detect the position of a substance from a fluorescent signal. In addition, a target-specific therapy was achieved through a photodynamic therapy effect (with or without a laser). Second, a nanoparticle composed of a near-infrared photosensitizer material was prepared and a tumor could then be detected using photoacoustic imaging. I also designed an experiment using local synergistic phototherapy based on the laser irradiation of loaded gemcitabine. In Chapter 1, a noninvasive and selective therapy (photodynamic therapy: PDT) is reviewed from wide research in clinical fields. The lower efficiency of PDT can induce unexpected side effects. Mitochondria have been researched extensively 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. Herein, is reported the development of a mitochondria-targeting photodynamic therapeutic agent (MitDt). This photosensitizer was synthesized from heptamethine cyanine dyes, which were conjugated or modified as follows. The heptamethine mesoposition was conjugated with a triphenylphosphonium derivative for mitochondrial targeting. The N-alkyl side chain was modified for regulation of charge balance and solubility, and the indolenine groups were brominated to enhance generation of reactive oxygen species (ROS) after laser irradiation. The synthesized MitDt increases the cancer uptake efficiency due to the lipo-cationic properties of the triphenylphosphonium. 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, related hypotheses were evaluated using in vitro and in vivo studies, and the results indicate strong potential for the use of MitDts as efficient single-molecule-based PDT agents for cancer treatment. In Chapter 2, it is explained how image-guided therapy, combined with multimodal imaging and therapeutic action, forms an attractive system because it can induce outstanding effects at focused locations. However, conventional liposomes cannot figure in therapeutic or imaging roles themselves, thereby inducing the disadvantage of their biological unavailability as a bio-photonic theragnosis tool. Therefore, I propose a novel multimodality imaging-guided chemo-thermotherapy system composed of phosphocholine conjugated C11 heptamethine cyanine dye with PEG conjugated heptamethine cyanine dye (NEPC). It is possible to simultaneously obtain chemotherapy and photothermal therapy (PTT) effects at the diagnosis site using photoacoustic imaging by loading the target with gemcitabine (NEPCG). The results indicated that the nanoparticle had a bilayer structure with high thermal efficacy. Furthermore, NEPC showed remarkable therapeutic efficacy only after laser irradiation. NEPCG has greater anticancer efficacy than free gemcitabine (GEM) does and more than NEPC with or without laser irradiation, due to the synergistic effect of PTT and chemotherapy. These unique properties offer a new approach to realize the multimodal potential of fluorophore nanoparticles as accurate and effective tools in clinical fields

테라그노시스 (Theragnosis) 는 therapy 와 diagnosis 의 합성어로써, 암 치료에서 조기 발견 및 치료를 할 수 있게 하여 환자의 생존율을 높일 수 있다는 점에서 많은 주목을 받고 있다. 현재, 질병 부분에 진단방법인 PA, CT, PET, 형광등을 이용하기 위한 유기 및 무기 물질 기반 테라그노시스템이 연구되어왔다. 이 중에서, 유기 시스템은 무기 시스템이 가지고 있는 생체적합성 및 독성문제를 극복할 수 있어서 많은 연구가 진행되어왔다. 특히, 근적외선 흡광을 가지는 형광체는 가시광선 영역보다 해상도와 contrast index가 높은 특성이 있다. 또한, 광치료 능력 (광역학 치료와 광열 치료)를 포함한 형광체의 능력을 통하여 전달된 국소 부위에 레이저의 유무에 따른 치료가 가능하게 한다. 따라서 나는 높은 해상도의 진단능력을 갖추고, 레이저에 따른 광치료 효과를 가능하게 하는 유기물 시스템을 개발했다. 이 학위논문에서, 나는 사이아닌 염료를 기반으로 한 물질을 구상하였으며, 두 가지 방향으로 연구했다. 첫 번째 연구는 암의 미토콘드리아를 표적으로 할 수 있는 단일 분자로써 형광 신호를 이용하여 위치를 파악할 수 있도록 설계했다. 이 물질은 레이저의 유무에 따라 암의 미토콘드리아에 광역학 치료를 선택적으로 할 수 있다. 두 번째는, 근적외선 형광체 물질 자체로 형성되는 나노입자를 준비했으며, 광음향 영상촬영을 통해 종양을 감지 할 수 있도록 설계했다. 또한, 젬시타빈을 나노입자에 탑재함으로써, 레이저의 유무에 따른 국소적인 시너지 효과를 가지는 광-화학 치료 효과를 얻을 수 있도록 설계했다.


청구기호 {DCBE 19031
형태사항 viii, 104 p. : 삽도 ; 30 cm
언어 영어
일반주기 저자명의 한글표기 : 노일구
지도교수의 영문표기 : Yeu-Chun Kim
지도교수의 한글표기 : 김유천
수록잡지명 : "Enhanced Photodynamic Cancer Treatment by Mitochondria-Targeting and Brominated Near-Infrared Fluorophores.". Advanced science, Volume 5, Issue 3, (2018)
학위논문 학위논문(박사) - 한국과학기술원 : 생명화학공학과,
서지주기 References : p. 94-98
주제 Cancer theragnosis
near-infrared photosensitizer
local therapy
cyanine dye
근적외선 형광체
사이아닌 염료
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