(220c) Tripartite Gold Nanoconjugate for Spinal Cord Injury Treatment: Targeting, Recovery, and Biodistribution

Respiratory problems are common and fatal consequences caused by spinal cord injury (SCI) in patients while systemic administrations of drugs that improve respiratory function cause harmful side effects. Gold nanoparticles (AuNPs) show promising potentials in biomedical applications regarding both diagnostic and therapeutic utilities. As a drug delivery carrier, AuNPs enable versatile conjugation chemistry with drugs and proteins and their size, shape, and surface chemistry can be precisely tuned. Despite the progress in nanomedicine our ability to target drugs to regions of disease remains to be very limited. This talk describes a tripartite nanoconjugate comprised of an AuNP drug carrier chemically conjugated to a transporter protein (wheat germ agglutinin coupled to horseradish peroxidase or WGA-HRP) and to SCI drugs such as theophylline. The nanoconjugate was synthesized by first reacting the thiol-protected AuNP with theophylline prodrug to form a biodegradable ester bond linkage. Then WGA-HRP was added to the nanoconjugate by the formation of an amide bond linkage. The final product’s chemical composition and nanostructure were characterized by UV-vis spectroscopy, transmission electron microscopy, dynamic light scattering, atomic force microscopy, and thermogravimetric analysis. The nanoconjugate therapeutic efficacy and biodistribution were studied in a validated animal model for hemidiaphragmatic spinal cord paralysis. Our results show that a single administration of the nanoconjugate improved diaphragmatic activity at a much lower dosage than the effective systemic drug dosage and restored the respiratory drive. The effects lasted for 14 days. A biodistribution study using inductively coupled plasma mass spectrometry on the same animal model shows that the nanoconjugate was successful in targeting the respiratory neurons in the medulla. This research demonstrates translational potential for SCI patients with respiratory dysfunction.