본 연구과제는 21세기 미래 혁신기술인 ‘분자영상’ 및 ‘나노의학’ 기술에 활용이 가능한 나노바이오 융합소재를 개발하여, 기존 의약품의 부작용을 최소화하고 진단/치료의 효율을 극대화하는 신규 나노의약품, 질병 진단용 나노 프로브, 환자 맞춤형 치료기술을 창출하여 국가 나노바이오 소재의 원천기술을 확보하고, 글로벌연구실을 통한 글로벌 협력 네트워크를 구축하여 최종적으로 나노바이오 소재 원천 기술개발의 글로벌 경쟁력을 확보하는 것을 목표로 2007년부터 2016년까지 총 9년 (3단계)로 구성되어 있으며, 1단계 (2007-2010)
본 연구과제는 21세기 미래 혁신기술인 ‘분자영상’ 및 ‘나노의학’ 기술에 활용이 가능한 나노바이오 융합소재를 개발하여, 기존 의약품의 부작용을 최소화하고 진단/치료의 효율을 극대화하는 신규 나노의약품, 질병 진단용 나노 프로브, 환자 맞춤형 치료기술을 창출하여 국가 나노바이오 소재의 원천기술을 확보하고, 글로벌연구실을 통한 글로벌 협력 네트워크를 구축하여 최종적으로 나노바이오 소재 원천 기술개발의 글로벌 경쟁력을 확보하는 것을 목표로 2007년부터 2016년까지 총 9년 (3단계)로 구성되어 있으며, 1단계 (2007-2010) 에서는 KIST 연구팀과 Purdue University 연구팀이 다양한 나노전달체 및 나노프로브를 개발하고 이들의 제조법 및 효능을 평가함. 1단계 연구에서는 암 표적성이 우수한 생체 고분자 기반 나노입자 광학 프로브를 개발하였으며, 광감작제가 봉입된 나노입자기반 항암치료제를 개발, 그 치료 효능을 검증함. 또한 고감도 분자영상을 위한 고효율 근적외 형광성 폴리머 닷 광학 프로브를 개발하고, 난치성 질환 치료를 위한 유전자 및 단백질 전달을 위한 나노팩토리 개발 그리고 적외선 열치료를 위한 나노바이오 닷 개발 및 영상시스템을 확립하였음. 2단계(2010-2013) 에서는 개발된 나노바이오 소재를 이용한 다양상성 영상화 및 다양한 난치성 질환 진단치료용 다기능성 나노전달체로서의 효능을 평가함. 2단계 연구에서는 MR/Optical, PET/Optical, CT/Optical의 다양상성 영상화 프로브의 개발 및 생체내 효소 활성도를 측정할 수 있는 프로브의 개발이 이루어짐. 또한 암 조직 특이성을 나타내는 나노입자 기반의 약물 전달형 융합소재의 개발, 다양한 질활에 선택성을 갖는 나노바이오 원천소재의 개발 및 치료 효능 평가 시스템 개발, 고효율, 표적형 유전자 전달체 개발 그리고 비천연당 도입을 통한 인공표적 수용체로 종양의 표적화 기술을 개발하여 질환의 진단 동시 치료 테라그노시스 소재의 개발 및 치료 효능을 최적화 함. 3단계 (2013-2016) 에서는 최적화된 나노바이오소재를 선정하고 이들의 최적화된 용법 및 진단/치료 효능의 최적화, 최적화된 프로토콜의 확립을 통한 나노바이오소재의 실용화를 실시함. 3단계 연구에서는 다양상성 이미징 프로브의 최적화된 영상화 프로토콜을 확립, 2종의 최적화된 나노바이오소재 선정, 종양축적성의 개선 및 선별된 소재의 대량생산법 확립 및 기술이전을 통한 소재의 실용화를 달성함. 본 연구과제를 수행하는 동안 연구결과의 우수성을 인정받아 세계수준의 SCI급 논문 64편 (IF>10이상 9편), 국내 출원/등록 특허 22편, 국외 출원/등록 특허 10편의 결과를 달성하였으며 해당연구를 통해 3건의 기술이전이 실시되어 국내 기업 및 Purdue University 내 기업을 통한 국내/외에서 산업화를 진행중에 있음.구
(출처 : 보고서 요약서 3p)
Abstract▼
Research Goal : To establish a new emerging technology "Theragnosis (Therapy + Diagnosis)” facilitated by nanomedicine and molecular imaging, we will develop highly advanced bio-active materials and early imaging diagnostic systems for theragnosis using nano-bio fusion technology through complementa
Research Goal : To establish a new emerging technology "Theragnosis (Therapy + Diagnosis)” facilitated by nanomedicine and molecular imaging, we will develop highly advanced bio-active materials and early imaging diagnostic systems for theragnosis using nano-bio fusion technology through complementary research collaborations.
Research Contents : 1st phase (2007-2009) ● Nano-Polymeric Particle Smart Probes for Fluorescence Optical Imaging: We developed various nano-probes which can be utilized for biomolecule detection and early diagnosis of diseases, i.e. cancer, in live animals. ● Highly Fluorescent NIR Polymer Dots for Optical Imaging: Highly fluorescent NIR polymer dots were synthesized and applied to sentinel lymph node imaging for metastasis diagnosis. ● Fusion Proteins for Drug Carrier: The Vector for programmable self-assembly peptide was designed and synthesized. Albumin based protein, with highly efficient and selective conjugation site, was designed and synthesized. ● Nano-Sized Drug Carriers for Nanomedicine: The therapeutic efficiency of photosensitizer loaded nanoparticle-based formulations were studied in vivo. ● Nano-Factory for Cell Engineering: Nanostructured gene containing carriers were imaged in real-time for nanomedicine. ● Nano-Bio Dot for Microwave Thermotherapy: Thermo sensitive gold nanoparticle-based nano-bio dot were developed and their therapeutic efficiency was evaluated.
2nd phase (2010-2012) ● Development of multi-modal imaging probes for early diagnosis of diseases - Multi-modal imaging probe for PET/Optical dual imaging: We designed new and smart multi-modal imaging probe for CT/Optical and PET/Optical imaging. - Multi-modal imaging probe for MR/optical imaging: The multi-modal imaging probes for MR/optical imaging were synthesized and applied in vivo for high sensitive diagnosis and anatomical information. - Multi-modal imaging probe for Ultrasound/optical imaging: We prepared new multi-modal imaging probes and gas generating macromolecules for US/optical imaging with high accessibility and high resolution. ● Development and characterization of smart nanomedicine delivery carrier for theragnosis - Development of therapeutic nanoparticles for nanomedicine: Real time imaging and screening of drug for disease were investigated with biocompatible chitosan and hyaluronic acid based nanoparticles. - Development of nano-sized delivery carrier for siRNA therapy: Design and characterization of nano-sized delivery carrier for siRNA. Real time imaging and stablility test of siRNA with carrier
3rd phase (2013-2015) ● Optimization and development of imaging protocols using multi-modal imaging probes for high-resolution multi-modal imaging · Optimization and development of imaging protocols for PET/Optical, MR/Optical dual imaging : We optimized MR/Optical dual imaging protocol and obtained high sensitive diagnosis and anatomical information in animal models using glycol chitosan nanoparticle based multi-modal probe. In addition, we also optimized PET/Optical dual imaging protocol to obtain high sensitive diagnosis and anatomical information in animal models. ● Development of multi-modal imaging protocol for disease-specific imaging probes · Optimization and development of imaging protocols for imaging of disease-specific enzyme activity using multi-modal probe : We optimized MMP-3 activity specific muti-modal imaging protocol using rheumatoid arthritis model. In addition, we showed disease specific biological changes in hind limb ischemia model using MMP-3 specific probe with EGFR probe. Finally, we optimized imaging protocol for tumor specific imaging using cathepsin B probe in various cancer animal models. ● Core technologies optimization of nano-bio materials for theragnosis · Improvement and optimization of theragnosis efficacy using glycol chitosan nanocarrier and hyaluronic acid nanocarrier : We performed comparative analysis of theragnosis efficacy between glycol chitosan nanocarrier/hyaluronic acid nanocarrier and other nanocarriers. · Optimization and development of theragnosis protocol using stimuli-responsive nano-bio materials : We optimized Ultrasound/Optical dual imaging protocol and obtained high sensitive diagnosis in animal models using gas-generating nano-bio materials based multi-modal probe. In addition we also optimized drug release profile using ultrasound stimuli resulting in improving tissue penetration and therapeutic efficacy in animal tumor model. ● Mass production and safety evaluation of nano-bio materials for optimizing usage · Optimization of usage of nano-bio materials based on the safety evaluation : We optimized usage of our nano-bio materials for theragnosis. In brief, we performed dose-dependent toxicity and safety evaluation of glycol chitosan nanoparticles in the cells (proliferation, gene expression) and animal model (tissue, blood). Glycol chitosan nanoparticles were not showed toxicities in animal model. · Confirmation of theragnostic effect of nano-bio materials in large animals : To the confirmation of theragnostic effect of our nano-bio materials in large animals, we performed NIRF imaging in tumor bearing rabbit model after treatment of glycol chitosan nanoparticles. · Technology transfer and mass production of nano-bio materials : We have transferred our nano-bio materials technology to the BioActs (Korea) and optimization of mass production protocols.
Expected Research Outputs : · We will establish the new approaches toward the theragnosis by developing novel nano-bio materials with global collaborations, raising the research fields of molecular imaging and nanomedicine to a new level to be internationally competitive. · Newly developed nano-bio fusion materials and innovative diagnosis tools for medical treatments will create high impact on the academic research and also generate new bio-industrial markets.
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