title: Transporter protein and drug-conjugated gold nanoparticles capable of bypassing the blood-brain barrier.
abstract: Drug delivery to the central nervous system (CNS) is challenging due to the inability of many drugs to cross the blood-brain barrier (BBB). Here, we show that wheat germ agglutinin horse radish peroxidase (WGA-HRP) chemically conjugated to gold nanoparticles (AuNPs) can be transported to the spinal cord and brainstem following intramuscular injection into the diaphragm of rats. We synthesized and determined the size and chemical composition of a three-part nanoconjugate consisting of WGA-HRP, AuNPs, and drugs for the treatment of diaphragm paralysis associated with high cervical spinal cord injury (SCI). Upon injection into the diaphragm muscle of rats, we show that the nanoconjugate is capable of delivering the drug at a much lower dose than the unconjugated drug injected systemically to effectively induce respiratory recovery in rats following SCI. This study not only demonstrates a promising strategy to deliver drugs to the CNS bypassing the BBB but also contributes a potential nanotherapy for the treatment of respiratory muscle paralysis resulted from cervical SCI.
authors.affiliation: Department of Chemical Engineering and Materials Science, Wayne State University, 5050 Anthony Wayne Drive, Detroit, MI 48202, USA.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Anatomy and Cell Biology, Wayne State University, 540 E Canfield St, Detroit, MI 48201, USA.
authors.forename: Janelle Buttry
authors.initials: JB
authors.lastname: Walker
authors.affiliation: Department of Anatomy and Cell Biology, Wayne State University, 540 E Canfield St, Detroit, MI 48201, USA.|Cardiovascular Research Institute, Wayne State University, 540 E Canfield St, Detroit, MI 48201, USA.
authors.forename: Zeljka
authors.initials: Z
authors.lastname: Minic
authors.affiliation: Department of Chemical Engineering and Materials Science, Wayne State University, 5050 Anthony Wayne Drive, Detroit, MI 48202, USA.
authors.forename: Fangchao
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Anatomy and Cell Biology, Wayne State University, 540 E Canfield St, Detroit, MI 48201, USA.
authors.forename: Harry
authors.initials: H
authors.lastname: Goshgarian
authors.affiliation: Department of Chemical Engineering and Materials Science, Wayne State University, 5050 Anthony Wayne Drive, Detroit, MI 48202, USA.
authors.forename: Guangzhao
authors.initials: G
authors.lastname: Mao
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier; D004576:Electromyography; D006046:Gold / Q000378:metabolism*; D006735:Horseradish Peroxidase / Q000378:metabolism*; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D017207:Rats, Sprague-Dawley; D013056:Spectrophotometry, Ultraviolet; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology; D013806:Theophylline / Q000737:chemistry / Q000494:pharmacology*; D014909:Wheat Germ Agglutinins / Q000378:metabolism*
chemical_list: D014909:Wheat Germ Agglutinins; D006046:Gold; D013806:Theophylline; D006735:Horseradish Peroxidase