title: Chlorotoxin Fused to IgG-Fc Inhibits Glioblastoma Cell Motility via Receptor-Mediated Endocytosis.
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.
authors.affiliation: Department of Medical and Bioengineering Science, Graduate School of Natural Science and Technology, Okayama University, Okayama 7008530, Japan.
authors.forename: Tomonari
authors.initials: T
authors.lastname: Kasai
authors.forename: Keisuke
authors.initials: K
authors.lastname: Nakamura
authors.forename: Arun
authors.initials: A
authors.lastname: Vaidyanath
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.forename: Sreeja
authors.initials: S
authors.lastname: Sekhar
authors.forename: Samah
authors.initials: S
authors.lastname: El-Ghlban
authors.forename: Masashi
authors.initials: M
authors.lastname: Okada
authors.forename: Akifumi
authors.initials: A
authors.lastname: Mizutani
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kudoh
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Murakami
authors.forename: Masaharu
authors.initials: M
authors.lastname: Seno