Polymer(Korea) (폴리머)

The Polymer Society of Korea (한국고분자학회)
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Preparation of PEG-Folate-graft-Polyethylenimine as a Gene Carrier

유전자 전달체로서 폴리(에틸렌 글리콜) 및 폴레이트로 수식된 폴리(에틸렌 이민)의 합성

  • Seo Dong Hoan (College Pharmacy, Sungkyunkwan University) ;
  • Kim Seon Hwa (Department of Advanced Organic Materials Engineering, Chonbuk National University) ;
  • Khang GilSon (Department of Advanced Organic Materials Engineering, Chonbuk National University) ;
  • Chi Sang Cheol (College Pharmacy, Sungkyunkwan University) ;
  • Shin Byung Cheol (Nanobiomaterials Laboratory, Korea Research Institute of Chemical Technology) ;
  • Kim Moon Suk (Nanobiomaterials Laboratory, Korea Research Institute of Chemical Technology)
  • 서동환 (성균관대학교 제약학과) ;
  • 김선화 (전북대학교 유기 신물질공학과) ;
  • 강길선 (전북대학교 유기 신물질공학과) ;
  • 지상철 (성균관대학교 제약학과) ;
  • 신병철 (한국화학연구원 화학소재부) ;
  • 김문석 (한국화학연구원 화학소재부)
  • Published : 2005.03.01
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Abstract

In this study, poly(ethylene imine) (PEI) modified by methoxypoly(ethylene glycol) (mPEG) and folate as a gene carrier was synthesized to decrease cytotoxicity and to improve in vivo targeting. mPEG was modified by glutaric anhydride (GA) to endow carboxylic end group, followed by the activation reaction with EDC (N-ethyl-N'-(3-dimethyl-aminopropyl) carbodiimide) and NHS (N-hydroxysuccinimide). The activated carboxylic end group of mPEG was reacted with the amines of PEI to give mPEG graft PEI. The mPEG-folate-graft-PEI was synthesized by the reaction of mPEG-PEI with folate pre-activated by EDC/NHS. The obtained copolymers were characterized by $^1H-NMR$ and FT-IR. Gel retardation assay and fluorescence measurement indicated that DNA formed the complexes with the synthesized copolymers above N/P charge ratio 2. The size of complexes was ranging from 100 nm to 300 m. In conclusion, we confirmed that the synthesized copolymer have the possibility as a DNA carrier.

본 연구에서는 세포 독성을 감소시키고 in vivo에서 표적화를 향상시키기 위하여 methoxypoly(ethylene glycol) (mPEG) 및 folate가 도입된 poly(ethylene imine)(PEI)를 합성하였다. mPEG 말단에 카복실 그룹을 도입하여 EDC/NHS에 의해 활성화시킨 후 PEI의 아민기와의 반응으로 mPEG-PEI를 합성하였다. Folate의 카복실 그룹을 EDC/NHS으로 활성화시킨 후 mPEG-PEI의 아민기와의 반응으로 PEG-folate-graft-PEI를 합성하였다. 합성된 고분자의 화학적 구조는 $^1H-NMR$과 H-n을 이용하여 확인하였다. 합성된 고분자와 DNA가 정전기적 인력에 의해 완전한 복합체의 형성을 확인하기 위해 여러 가지 N/P charge 비율로 agarose gel 전기영동 및 형광을 측정하였고, 2 이상의 N/P charge 비율에서 완전한 복합체를 형성함을 확인하였다. 복합체의 크기는 광산란장치 및 AFM으로부터 $100\~300nm$임을 관찰하였다. 이러한 결과들로부터 합성된 양이온성 고분자와 DNA가 복합체를 잘 이루어지는 것을 관찰하였고 유전자 전달체로서의 가능성을 평가하고자 하였다.

Keywords

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