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

Hongshan Liang,1–3 Bin Zhou,4 Yun He,1–3 Yaqiong Pei,1–3 Bin Li,1–3 Jing Li1–31College of Food Science and Technology, Huazhong Agricultural University, 2Key Laboratory of Environment Correlative Dietology, Huazhong Agricultural University, Ministry of Education, 3Functional Food Engineering & Technology Research Center of Hubei Province, Wuhan, Hubei, 4College of Food Science and Technology, Shanghai Ocean University, LinGang New City, Shanghai, People’s Republic of ChinaAbstract: 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. Keywords: coordination bonding, pH-responsive, high stimulus sensitivity, drug delivery