title: In vivo tumor targeting by the B-subunit of shiga toxin.
abstract: Delivery of drugs to the appropriate target cells would improve efficacy and reduce potential side effects. The nontoxic B-subunit of the intestinal pathogen-produced Shiga toxin (STxB) binds specifically to the glycosphingolipid Gb3, overexpressed in membranes of certain tumor cells, and enters these cells through the retrograde pathway. Therefore, STxB binding to Gb3 receptors may be useful for cell-specific vectorization or imaging purposes. Here we labeled STxB with a fluorophore to evaluate its potential as an in vivo cell-specific targeting reagent in two different models of human colorectal carcinoma. Fluorescent STxB was administered systemically to xenografted nude mice, and its biodistribution was studied by optical imaging. The use of fluorescent STxB allowed the combination of the macroscopic observations with analyses at the cellular level using confocal microscopy. After administration, the fluorescent STxB was slowly eliminated by renal excretion. However, it accumulated in the tumor area. Furthermore, STxB was demonstrated to enter the Gb3-expressing tumoral cells, as well as the epithelial cells of the neovascularization and the monocytes and macrophages surrounding the xenografts.
authors.affiliation: Laboratoire d'Imagerie Moléculaire Expérimentale, Commissariat à l'Energie Atomique, Institut d'Imagerie Biomédicale, Orsay, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Viel
authors.forename: Estelle
authors.initials: E
authors.lastname: Dransart
authors.forename: Fariba
authors.initials: F
authors.lastname: Nemati
authors.forename: Emilie
authors.initials: E
authors.lastname: Henry
authors.forename: Benoit
authors.initials: B
authors.lastname: Thézé
authors.forename: Didier
authors.initials: D
authors.lastname: Decaudin
authors.forename: Daniel
authors.initials: D
authors.lastname: Lewandowski
authors.forename: Raphael
authors.initials: R
authors.lastname: Boisgard
authors.forename: Ludger
authors.initials: L
authors.lastname: Johannes
authors.forename: Bertrand
authors.initials: B
authors.lastname: Tavitian
mesh_terms: D000284:Administration, Oral; D000818:Animals; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D051379:Mice; D008819:Mice, Nude; D021122:Protein Subunits / Q000494:pharmacology*; D022603:Shiga Toxins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
chemical_list: D021122:Protein Subunits; D022603:Shiga Toxins