화학공학소재연구정보센터
홈 로그인 로그아웃 연락처 사이트맵
Polymer(Korea), Vol.30, No.4, 279-285, July, 2006
Export Citation
저분자량 수용성 키토산을 이용한 동맥 벽 표적성 유전자 전달체의 합성
The Synthesis of Artery Wall Targeted Gene Carrier Using Low Molecular Water-Soluble Chitosan
최창용, 장미경, 나재운†
  • 순천대학교 공과대학 신소재응용공학부
Changyong Choi, Mi-Kyeong Jang, and Jae-Woon Nah†
  • Department of Polymer Science and Engineering, College Engineering, Sunchon National University, Jeonnam 540-742, Korea
E-mail:
초록
유전자 치료에 있어서 안전성의 장점을 지니고 있는 비바이러스성 전달체에 대한 관심도가 높아져가고 있다. 비바이러스성 전달체 중, 양이온성 리포좀이나 합성 유전자 전달체는 in vitro계에서 효율적인 DNA 전달체이지만, 낮은 생체적합성으로 인하여 in vivo계에서의 응용성은 크게 뒤떨어지고 있다. 한편, 천연 양이온성 다당류인 키토산은 낮은 독성과 강한 양전하를 띠고 있어 유전자 전달 시스템(gene delivery system)에 있어 아주 기대되는 전달체이다. 본 연구에서는 저분자량 수용성 키토산(low molecular water-soluble chitosan ; LMWSC)을 이용하여 동맥 벽 세포를 표적할 수 있는 표적성 유전자 전달체를 합성하였다. 상대 점도와 Kina 적정법을 이용하여 LMWSC의 점도 평균 분자량(Mw)과 탈아세틸화도(degree of deacetylation；DDA)를 측정하였고 구조는 FTIR, 1H-NMR, 그리고 13C-NMR을 통하여 분석하였다. 동맥 벽을 표적하기 위한 유전자 전달체로서 pegylated LMWSC의 말단에 특이성 세포 표적 펩타이드인 artery wall binding peptide(AWBP)를 결합시킴으로써 AWBP-PEG-g-LMWSC을 합성하였고 FTIR, 1H-NMR, zeta potentiometer, 그리고 atomic force microscopy(AFM)을 이용하여 분석하였다.
Non-viral gene carriers continue to attract a great deal of interest due to advantageous safety profile. Among the non-viral gene carriers, cationic liposomes or synthetic gene carriers are efficient DNA carriers in vitro, but their in vivo applications are greatly hampered because of low biocompatibility. On the other hand, chitosan, a natural cationic polysaccharide, is a candidate non-viral vector for gene delivery because of its low cytotoxicity and high positive charges. In this work, targeted gene carrier was synthesized to target artery wall cells using low molecular water-soluble chitosan (LMWSC). The molecular weight(Mw) and degree of deacetylation(DDA) of LMWSC were measured by relative viscometer and Kina titration, respectively. The structure of LMWSC was analyzed by measuring FTIR, 1H-NMR, and 13C-NMR. AWBP-PEG-g-LMWSC was synthesized by conjugation of the artery wall binding peptide(AWBP), a specific targeting peptide, to the end of pegylated LMWSC as a gene carrier to target artery wall cells. The synthesized AWBP-PEG-g-LMWSC were analyzed by measuring FTIR, 1H-NMR, zeta-potentiometer, and atomic force microscopy(AFM).
Keywords:low molecular water-soluble chitosan(LMWSC);artery wall binding peptide(AWBP);N- hydroxysuccinimide polyethylene glycol vinylsulfone(NHS-PEG-VS);non-viral vector
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