Biofabricated nanoparticle coating for liver-cell targeting.

Abstract

Biology routinely uses noncovalent interactions to perform complex functions that range from the molecular recognition of ligand-receptor binding to the reversible self-assembly/disassembly of hierarchical nanostructures (e.g., virus particles). Potentially, biological materials that offer such recognition and reversible self-assembly functionality can be applied to nanomedicine. Here, polysaccharides with the multifunctional polysaccharide-binding protein Concanavalin A (Con A) are coupled to create a functional nanoparticle coating. This coating is self-assembled in a layer-by-layer format by sequentially contacting a nanoparticle with Con A and the polysaccharide glycogen. In the final assembly step, a galactomannan targeting ligand is self-assembled into the coating. Evidence indicates that the mannose residues of the galactomannan backbone are responsible for assembly into the coating by Con A binding, while the galactose side chain residues are responsible for targeting to the liver-specific asialoglycoprotein receptor (ASGP-R). Binding to ASGP-R induces endocytic uptake, while the low endosomal pH triggers disassembly of the coating and release of the nanoparticle-entrapped drug. In vitro cell studies indicate that the coating confers liver-cell-specific function for both nanoparticle uptake and drug delivery. These studies extend the use of Con A to sugar-mediated and organ-specific targeting, and further illustrate the potential of biologically based fabrication for generating functional materials.