title: Glycoprotein CD98 as a receptor for colitis-targeted delivery of nanoparticle.
abstract: Treatment strategies for inflammatory bowel disease have been constrained by limited therapeutic efficacy and serious adverse effects owing to a lack of receptor for targeted drug delivery to the inflamed colon. Upon inflammation, CD98 expression is highly elevated in colonic epithelial cells and infiltrating immune cells. To investigate whether CD98 can be used as a colitis-targeted delivery receptor, we constructed CD98 Fab'-bearing quantum dots (QDs)-loaded nanoparticles (Fab'-NPs). The resultant Fab'-NPs had desired particle size (~458 nm) with a narrow size distribution and zeta-potential (approximately +19 mV), low cytotoxicity, and excellent fluorescence properties. Electron microscopy images provided direct evidence for the well-dispersed distribution of QDs within spherical Fab'-NPs. Cellular uptake experiments demonstrated that Fab'-NPs were efficiently internalized into Colon-26 and RAW 264.7 cells through the CD98-mediated endocytosis pathway, and showed that the targeting effect of CD98 Fab' markedly increased their cellular uptake efficiency compared with control pegylated QDs-loaded NPs (PEG-NPs). Furthermore,ex vivostudies showed much more effective accumulation of Fab'-NPs in colitis tissue than that of PEG-NPs. These findings suggest that because of inflammation-dependent over-expression of CD98, active colitis-targeted delivery can be accomplished using NPs decorated with CD98 antibody.
authors.affiliation: Center for Diagnostics and Therapeutics, Department of Biology and Chemistry, Georgia State University, Atlanta, 30302, USA. ; Tel: +1-404-413-3597.
authors.forename: Bo
authors.initials: B
authors.lastname: Xiao
authors.affiliation: Center for Diagnostics and Therapeutics, Department of Biology and Chemistry, Georgia State University, Atlanta, 30302, USA. ; Tel: +1-404-413-3597.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Center for Diagnostics and Therapeutics, Department of Biology and Chemistry, Georgia State University, Atlanta, 30302, USA. ; Tel: +1-404-413-3597 ; Atlanta Veterans Affairs Medical Center, Decatur, 30033, USA.
authors.forename: Emilie
authors.initials: E
authors.lastname: Viennois
authors.affiliation: Center for Diagnostics and Therapeutics, Department of Biology and Chemistry, Georgia State University, Atlanta, 30302, USA. ; Tel: +1-404-413-3597.
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Center for Diagnostics and Therapeutics, Department of Biology and Chemistry, Georgia State University, Atlanta, 30302, USA. ; Tel: +1-404-413-3597.
authors.forename: Saravanan
authors.initials: S
authors.lastname: Ayyadurai
authors.affiliation: Center for Diagnostics and Therapeutics, Department of Biology and Chemistry, Georgia State University, Atlanta, 30302, USA. ; Tel: +1-404-413-3597.
authors.forename: Mark
authors.initials: M
authors.lastname: Baker
authors.affiliation: Center for Diagnostics and Therapeutics, Department of Biology and Chemistry, Georgia State University, Atlanta, 30302, USA. ; Tel: +1-404-413-3597.
authors.forename: Hamed
authors.initials: H
authors.lastname: Laroui
authors.affiliation: Center for Diagnostics and Therapeutics, Department of Biology and Chemistry, Georgia State University, Atlanta, 30302, USA. ; Tel: +1-404-413-3597 ; Atlanta Veterans Affairs Medical Center, Decatur, 30033, USA.
authors.forename: Didier
authors.initials: D
authors.lastname: Merlin
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