Tailoring stimuli-responsive delivery system driven by metal–ligand coordination bonding

In this study, a novel coordination bonding system based on metal-tannic acid (TA) architecture on zein/carboxymethyl chitosan (CMCS) nanoparticles (NPs) was investigated for the pH-responsive drug delivery. CMCS has been reported to coat on zein NPs as delivery vehicles for drugs or nutrients in previous studies. The cleavage of either the "metal-TA" or "NH2-metal" coordination bonds resulted in significant release of guest molecules with high stimulus sensitivity, especially in mild acidic conditions. The prepared metal-TA-coated zein/CMCS NPs (zein/CMCS-TA/metal NPs) could maintain particle size in cell culture medium at 37°C, demonstrating good stability compared with zein/CMCS NPs. In vitro release behavior of doxorubicin hydrochloride (DOX)-loaded metal-TA film-coated zein/CMCS NPs (DOX-zein/CMCS-TA/metal NPs) showed fine pH responsiveness tailored by the ratio of zein to CMCS as well as the metal species and feeding concentrations. The blank zein/CMCS-TA/metal NPs (NPs-TA/metal) were of low cytotoxicity, while a high cytotoxic activity of DOX-zein/CMCS-TA/metal NPs (DOX-NPs-TA/metal) against HepG2 cells was demonstrated by in vitro cell assay. Confocal laser scanning microscopy (CLSM) and flow cytometry were combined to study the uptake efficiency of DOX-NPs or DOX-NPs-TA/metal. This system showed significant potential as a highly versatile and potent platform for drug delivery.