Interfacial Interactions between Neural Tracing Lectin–Gold Nanoparticle Conjugate and Cell Membrane Glycoproteins

The use of neural tracers as targeting molecules for drug delivery has been previously established as a novel and efficient method of neural drug delivery. The wheat germ agglutinin–horseradish peroxidase conjugate (WGAHRP) is a common neural tracer, which has been used extensively to decipher neural pathways in vertebrates. It has been widely reported to bind to cell surfaces and be transported in a retrograde fashion (from synapses toward the cell body) via dynein motors along microtubules within axons and transynaptically between neurons. Here we report on the differential binding between WGAHRP and gold-conjugated WGAHRP (AuNP-WGAHRP) to the glycoprotein profiles extracted from two neuronal cell lines and one skeletal muscle cell line, as well as the binding kinetics to heparin. From proteomic analysis of the extracted glycoproteins, we suggest the identity of cell surface glycoproteins involved in the retrograde transport of WGAHRP. This study illuminates the interfacial and molecular interactions of protein–gold conjugates with native ligands and opens the door for the identification of new targets for neural tracing and nervous system-related drug delivery.