title: Efficient CRM197-mediated drug targeting to monocytes.
abstract: Efficient delivery of drugs to specific cellular reservoirs is of particular importance for therapeutics that are not able to pass cellular barriers and that may have unwanted side effects in off-target tissues. Heparin-binding epidermal growth factor (HB-EGF) is expressed on leukocytes and may be targeted for specific drug delivery using cross-reacting material (CRM)197, a non-toxic variant of diphtheria toxin and exogenous substrate for HB-EGF. We used fluorescently labeled CRM197 and CRM197-coated liposomes to investigate their potential use for drug delivery to leukocytes. We demonstrate that CRM197-guided systems are efficiently taken up by human leukocytes in vitro. CRM197 was also found to specifically target leukocytes in vivo in mice with components of the human immune system (HIS mice) and hamsters. Monocytes represent the most prominent subset of leukocytes that showed highly specific CRM197-mediated uptake. We therefore propose the application of CRM197 as a novel targeting approach in diseases that require the selective treatment of monocytes.
authors: Division of Pharmacology, Leiden/Amsterdam Centre for Drug Research, Leiden University, Leiden, The Netherlands. g.schenk@VUMC.nl
authors: Geert J
authors: GJ
authors: Schenk
authors: P C Joost
authors: PC
authors: Haasnoot
authors: Mireille
authors: M
authors: Centlivre
authors: Nicolas
authors: N
authors: Legrand
authors: Jaap
authors: J
authors: Rip
authors: Albertus G
authors: AG
authors: de Boer
authors: Ben
authors: B
authors: Berkhout
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000008:administration & dosage*; D002460:Cell Line; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D016503:Drug Delivery Systems; D005260:Female; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D053631:Interleukin Receptor Common gamma Subunit / Q000172:deficiency / Q000235:genetics; D008081:Liposomes; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D053631:Interleukin Receptor Common gamma Subunit; D008081:Liposomes; C499308:Rag2 protein, mouse; C028581:CRM197 (non-toxic variant of diphtheria toxin)