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김종호
김종호 (Jong-Ho Kim) 저자 이메일 보기
한국과학기술연구원
조회 785  인쇄하기 주소복사 트위터 공유 페이스북 공유 
Self-assembled glycol chitosan nanoparticles for the sustained and prolonged delivery of antiangiogenic small peptide drugs in cancer therapy
Jong-Ho Kima, 1, Yoo-Shin Kimb, 1, Kyeongsoon Parka, Eunah Kanga, Seulki Leea, Hae Yun Nama, c, Kwangmeyung Kima, Jae Hyung Parkc, Dae Yoon Chid, Rang-Woon Parkb, In-San Kimb, Kuiwon Choia, Ick Chan Kwona,*

a Biomedical Research Center, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791, Republic of Korea
b Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, 101 Dongin-Dong, Jung-Gu, Daegu 700-422, Republic of Korea
c Department of Advanced Polymer and Nanopharmaceutical Sciences, Kyung Hee University, 1 Seocheon-dong, Giheung-gu, Yongin-Si, Gyeonggi-do 449-701, Republic of Korea
d Department of Chemistry, Inha University, 253 Yonghyundong, Namgu, Inchon 402-751, Republic of Korea
1 These authors contributed equally to this paper.

*Corresponding author : Ick Chan Kwon

Abstract
Antiangiogenic peptide drugs have received much attention in the fields of tumor therapy and tumor imaging because they show promise in the targeting of integrins such as αvβ3 on angiogenic endothelial cells. However, systemic antiangiogenic peptide drugs have short half-lives in vivo, resulting in fast serum clearance via the kidney, and thus the therapeutic effects of such drugs remain modest. In this study, we prepared self-assembled glycol chitosan nanoparticles and explored whether this construct might function as a prolonged and sustained drug delivery system for RGD peptide, used as an antiangiogenic model drug in cancer therapy. Glycol chitosan hydrophobically modified with 5β-cholanic acid (HGC) formed nanoparticles with a diameter of 230 nm, and RGD peptide was easily encapsulated into HGC nanoparticles (yielding RGD-HGC nanoparticles) with a high loading efficiency (>85%). In vitro work demonstrated that RGD-HGC showed prolonged and sustained release of RGD, lasting for 1 week. RGD-HGC also inhibited HUVEC adhesion to a βig-h3 protein-coated surface, indicating an antiangiogenic effect of the RGD peptide in the HGC nanoparticles. In an in vivo study, the antiangiogenic peptide drug formulation of RGD-HGC markedly inhibited bFGF-induced angiogenesis and decreased hemoglobin content in Matrigel plugs. Intratumoral administration of RGD-HGC significantly decreased tumor growth and microvessel density compared to native RGD peptide injected either intravenously or intratumorally, because the RGD-HGC formulation strongly enhanced the antiangiogenic and antitumoral efficacy of RGD peptide by affording prolonged and sustained RGD peptide delivery locally and regionally in solid tumors.

Keywords : Glycol chitosan nanoparticles; Drug delivery system; Antiangiogenic peptide drugs; Cancer therapy

논문정보
- 형식: Research article
- 게재일: 2008년 04월 (BRIC 등록일 2015-11-20)
- 연구진: 국내연구진태극기
- 분야: Biochemistry, Pharmacology
- 피인용횟수: 120회 이상 인용된 논문
Dot/Icm 제 4 유형 커플링 단백질 복합체의 선택적 이펙터 단백질 인식[Nat. Commun.]
김현민
발표: 김현민 (KAIST)
일자: 2020년 9월 29일 (화) 오후 02시 (한국시간)
언어: 한국어
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