Catechol-modified stabilizer facilitates impulsive ligand functionalization of particulates and membrane modification of cells

Abstract

Ligand-functionalized particulates have received considerable attention for targeted drug delivery. Previous studies have reported several methods for functionalizing various molecules on the surfaces of nano- and micro- particulates which involve multiple steps, reaction buffers and chemicals, and long reaction times. Here, we report a single-step method that uses catechol chemistry to rapidly functionalize ligands on the surfaces of polymeric nanoparticles (NPs). We synthesized dopamine-conjugated poly (ethylene-alt-maleic alt- maleic acid) (D-PEMA) by performing a nucleophilic addition reaction between dopamine and poly (ethylene-alt-maleic alt-maleic anhydride) (PEMAnh). We then used D-PEMA as a stabilizer while preparing NPs which led to the construction of NPs that were non-adhesive per se but provided active sites for conjugating multiple different ligands in an alkaline buffer via Michael's addition and Schiff's base substitution reactions. The ligand-functionalized NPs were nontoxic and effectively internalized by both primary and cancer cells. In addition, NPs prepared using the modified stabilizer conjugated rapidly on the surfaces of pancreatic islets in alkaline conditions. Our study provides evidence that the modified stabilizer is versatile and has the potential for drug delivery applications and cell surface modifications.