Self-assembled glycol chitosan nanoparticles for the sustained and prolonged delivery of antiangiogenic small peptide drugs in cancer therapy

Jong Ho Kim, Yoo Shin Kim, Kyeongsoon Park, Eunah Kang, Seulki Lee, Hae Yun Nam, Kwangmeyung Kim, Jae Hyung Park, Dae Yoon Chi, Rang Woon Park, In San Kim, Kuiwon Choi, Ick Chan Kwon

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188 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1920-1930
Number of pages11
JournalBiomaterials
Volume29
Issue number12
DOIs
Publication statusPublished - 2008 Apr

Keywords

  • Antiangiogenic peptide drugs
  • Cancer therapy
  • Drug delivery system
  • Glycol chitosan nanoparticles

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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  • Cite this

    Kim, J. H., Kim, Y. S., Park, K., Kang, E., Lee, S., Nam, H. Y., Kim, K., Park, J. H., Chi, D. Y., Park, R. W., Kim, I. S., Choi, K., & Chan Kwon, I. (2008). Self-assembled glycol chitosan nanoparticles for the sustained and prolonged delivery of antiangiogenic small peptide drugs in cancer therapy. Biomaterials, 29(12), 1920-1930. https://doi.org/10.1016/j.biomaterials.2007.12.038