Chlorotoxin Fused to IgG-Fc Inhibits Glioblastoma Cell Motility via Receptor-Mediated Endocytosis. (5th December 2012)

• Record Type: Journal Article
• Authors: Kasai, Tomonari; Nakamura, Keisuke; Vaidyanath, Arun; Chen, Ling; Sekhar, Sreeja; El-Ghlban, Samah; Okada, Masashi; Mizutani, Akifumi; Kudoh, Takayuki; Murakami, Hiroshi; Seno, Masaharu
• Other Names: Tzakos Andreas G. Academic Editor.
• Is Part Of: Journal of drug delivery. Volume 2012(2012)
• Publication Date: 2012-12-05
• Subjects: Drug delivery systems -- Periodicals; 615.605
• DOI: 10.1155/2012/975763
• Languages: English
• ISSNs: 2090-3014

Abstract

Abstract : Chlorotoxin is a 36-amino acid peptide derived from Leiurus quinquestriatus (scorpion) venom, which has been shown to inhibit low-conductance chloride channels in colonic epithelial cells. Chlorotoxin also binds to matrix metalloproteinase-2 and other proteins on glioma cell surfaces. Glioma cells are considered to require the activation of matrix metalloproteinase-2 during invasion and migration. In this study, for targeting glioma, we designed two types of recombinant chlorotoxin fused to human IgG-Fcs with/without a hinge region. Chlorotoxin fused to IgG-Fcs was designed as a dimer of 60 kDa with a hinge region and a monomer of 30 kDa without a hinge region. The monomeric and dimeric forms of chlorotoxin inhibited cell proliferation at 300 nM and induced internalization in human glioma A172 cells. The monomer had a greater inhibitory effect than the dimer; therefore, monomeric chlorotoxin fused to IgG-Fc was multivalently displayed on the surface of bionanocapsules to develop a drug delivery system that targeted matrix metalloproteinase-2. The target-dependent internalization of bionanocapsules in A172 cells was observed when chlorotoxin was displayed on the bionanocapsules. This study indicates that chlorotoxin fused to IgG-Fcs could be useful for the active targeting of glioblastoma cells.