title: Peptide-functionalized polymeric nanoparticles for active targeting of damaged tissue in animals with experimental autoimmune encephalomyelitis.
abstract: Increased permeability of blood vessels is an indicator for various injuries and diseases, including multiple sclerosis (MS), of the central nervous system. Nanoparticles have the potential to deliver drugs locally to sites of tissue damage, reducing the drug administered and limiting associated side effects, but efficient accumulation still remains a challenge. We developed peptide-functionalized polymeric nanoparticles to target blood clots and the extracellular matrix molecule nidogen, which are associated with areas of tissue damage. Using the induction of experimental autoimmune encephalomyelitis in rats to provide a model of MS associated with tissue damage and blood vessel lesions, all targeted nanoparticles were delivered systemically. In vivo data demonstrates enhanced accumulation of peptide functionalized nanoparticles at the injury site compared to scrambled and naive controls, particularly for nanoparticles functionalized to target fibrin clots. This suggests that further investigations with drug laden, peptide functionalized nanoparticles might be of particular interest in the development of treatment strategies for MS.
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Queensland, Australia; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Canada. Electronic address: tobias.fuehrmann@utoronto.ca.
authors.forename: Tobias
authors.initials: T
authors.lastname: Führmann
authors.affiliation: The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.
authors.forename: Mousumi
authors.initials: M
authors.lastname: Ghosh
authors.affiliation: The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Otero
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Queensland, Australia.
authors.forename: Ben
authors.initials: B
authors.lastname: Goss
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Queensland, Australia.
authors.forename: Tim R
authors.initials: TR
authors.lastname: Dargaville
authors.affiliation: The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL, 33136, USA; The Department of Neurological Surgery, The Neuroscience Program, The Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.
authors.forename: Damien D
authors.initials: DD
authors.lastname: Pearse
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Queensland, Australia; Department of Functional Materials in Medicine and Dentistry, University of Würzburg, Würzburg, Germany.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Dalton
mesh_terms: D000818:Animals; D002232:Carbocyanines / Q000008:administration & dosage / Q000737:chemistry; D004337:Drug Carriers; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D005337:Fibrin / Q000737:chemistry / Q000378:metabolism; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D007783:Lactones / Q000737:chemistry; D007797:Laminin / Q000737:chemistry; D008562:Membrane Glycoproteins / Q000378:metabolism; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000378:metabolism; D053758:Nanoparticles; D009842:Oligopeptides / Q000008:administration & dosage* / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D011916:Rats, Inbred F344; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C582073:1,1'-dioleyl-3,3,3',3'-tetramethylindocarbocyanine; D002232:Carbocyanines; D004337:Drug Carriers; D005456:Fluorescent Dyes; D007783:Lactones; D007797:Laminin; D008562:Membrane Glycoproteins; D009842:Oligopeptides; C029967:nidogen; C473831:poly(ethylene oxide)-b-poly(caprolactone); D011092:Polyethylene Glycols; C098044:3,3'-dioctadecyloxacarbocyanine; D005337:Fibrin
keywords: Multiple sclerosis; Nanoparticles; Spinal cord; Targeted delivery