Engineering Multifunctional Coatings on Nanoparticles Based on Oxidative Coupling Assembly of Polyphenols for Stimuli-Responsive Drug Delivery

In this study, zein nanoparticles (NPs) with novel multifunctional coatings based on oxidative coupling assembly of polyphenols were synthesized for the first time. This coating was formed by oxidative self-polymerization of the organic ligands (polyphenols) in an alkaline condition, which could be biodegraded by acidic pH, as a result, impacting the pH-responsive property of the system. More importantly, the high level of intracellular glutathione (GSH) could induce the biodegradation of the polyphenol coatings, resulting in a fast release of trapped anticancer drugs in the cells. Based on confocal laser scanning microscopy (CLSM) and cytotoxicity experiments, drug-loaded and polyphenol-coated zein NPs were shown to possess highly efficient internalization and an apparent cytotoxic effect on HeLa cells. Notably, the CLSM observation illustrated that coated zein NPs showed delayed drug release compared with free drug or DOX-loaded zein NPs without coatings, resulting from the pH-responsive release of loaded drug in the extra/intracellular environment. Additionally, the short-time cytotoxicity and morphology observation also confirmed the delayed drug release behavior of coated NPs. These highly biocompatible and biodegradable polyphenol-coated zein NPs may be promising vectors in the field of controlled-release biomedical applications and cancer therapy.