title: Development of siRNA-loaded chitosan nanoparticles targeting Galectin-1 for the treatment of glioblastoma multiforme via intranasal administration.
abstract: Galectin-1 (Gal-1) is a naturally occurring galactose-binding lectin, which is overexpressed in glioblastoma multiforme (GBM). Gal-1 is associated with tumor progression, and is a potent immune suppressor in the tumor micro-environment. To inhibit Gal-1 in GBM, an effective therapy is required that reaches the central nervous system tumor, with limited systemic effects. In this study, we report for the first time that concentrated chitosan nanoparticle suspensions can deliver small interfering RNA (siRNA) into the central nervous system tumor within hours after intranasal administration. These nanoparticles are able to complex siRNA targeting Gal-1 to a high percentage, and protect them from RNAse degradation. Moreover, a successful intracellular delivery of anti-Gal-1 siRNA resulted in a decreased expression of Gal-1 in both murine and human GBM cells. Sequence specific RNAinterference, resulted in more than 50% Gal-1 reduction in tumor bearing mice. This study indicates that the intranasal pathway is an underexplored transport route for delivering siRNA-based therapies targeting Gal-1 in the treatment of GBM.
authors.affiliation: Research Group Experimental Neurosurgery and Neuroanatomy, KU Leuven, Herestraat 49, Leuven 3000, Belgium; Laboratory of Pharmaceutics and Biopharmaceutics, Faculté de Pharmacie, Université Libre de Bruxelles (ULB), Bvd du triomphe CP207, Brussels 1050, Belgium. Electronic address: Matthias.vanwoensel@med.kuleuven.be.
authors.forename: Matthias
authors.initials: M
authors.lastname: Van Woensel
authors.affiliation: Laboratory of Pharmaceutics and Biopharmaceutics, Faculté de Pharmacie, Université Libre de Bruxelles (ULB), Bvd du triomphe CP207, Brussels 1050, Belgium.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Wauthoz
authors.affiliation: Laboratory of Pharmaceutics and Biopharmaceutics, Faculté de Pharmacie, Université Libre de Bruxelles (ULB), Bvd du triomphe CP207, Brussels 1050, Belgium.
authors.forename: Rémi
authors.initials: R
authors.lastname: Rosière
authors.affiliation: Laboratoire de Cancérologie et de Toxicologie Expérimentale, Faculté de Pharmacie, ULB, Bvd du triomphe CP207, Brussels 1050, Belgium.
authors.forename: Véronique
authors.initials: V
authors.lastname: Mathieu
authors.affiliation: Laboratoire de Cancérologie et de Toxicologie Expérimentale, Faculté de Pharmacie, ULB, Bvd du triomphe CP207, Brussels 1050, Belgium.
authors.forename: Robert
authors.initials: R
authors.lastname: Kiss
authors.affiliation: Department of Neurosurgery, Erasmus University Hospitals, Brussels 1050, Belgium.
authors.forename: Florence
authors.initials: F
authors.lastname: Lefranc
authors.affiliation: Laboratory of Clinical Immunology, KU Leuven, Herestraat 49 box 811, Leuven 3000, Belgium.
authors.forename: Brecht
authors.initials: B
authors.lastname: Steelant
authors.affiliation: Laboratory of Clinical Immunology, KU Leuven, Herestraat 49 box 811, Leuven 3000, Belgium.
authors.forename: Ellen
authors.initials: E
authors.lastname: Dilissen
authors.affiliation: Laboratory of Pediatric Immunology, KU Leuven, Herestraat 49 box 811, Leuven 3000, Belgium.
authors.forename: Stefaan W
authors.initials: SW
authors.lastname: Van Gool
authors.affiliation: Vascular Patterning Laboratory (Vesalius Research Center), VIB, Leuven 3000, Belgium.
authors.forename: Thomas
authors.initials: T
authors.lastname: Mathivet
authors.affiliation: Vascular Patterning Laboratory (Vesalius Research Center), VIB, Leuven 3000, Belgium.
authors.forename: Holger
authors.initials: H
authors.lastname: Gerhardt
authors.affiliation: Laboratory of Pharmaceutics and Biopharmaceutics, Faculté de Pharmacie, Université Libre de Bruxelles (ULB), Bvd du triomphe CP207, Brussels 1050, Belgium.
authors.forename: Karim
authors.initials: K
authors.lastname: Amighi
authors.affiliation: Research Group Experimental Neurosurgery and Neuroanatomy, KU Leuven, Herestraat 49, Leuven 3000, Belgium; Department of Neurosurgery, University Hospitals Leuven, Herestraat 49, Leuven 3000, Belgium.
authors.forename: Steven
authors.initials: S
authors.lastname: De Vleeschouwer
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D005260:Female; D037483:Galectin 1 / Q000235:genetics*; D005909:Glioblastoma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics / Q000627:therapeutic use; D000067492:RNAi Therapeutics / Q000379:methods
chemical_list: D004337:Drug Carriers; D037483:Galectin 1; D034741:RNA, Small Interfering; D048271:Chitosan
keywords: Chitosan; Galectin-1; Glioblastoma; Intranasal; Nanoparticles; siRNA