Encapsulation of Hydrophobic Drugs in Shell-by-Shell Coated Nanoparticles for Radio—and Chemotherapy—An In Vitro Study

Our research objective was to develop novel drug delivery vehicles consisting of TiO2 and Al2O3 nanoparticles encapsulated by a bilayer shell that allows the reversible embedment of hydrophobic drugs. The first shell is formed by covalent binding of hydrophobic phosphonic acid at the metal oxide surface. The second shell composed of amphiphilic sodium dodecylbenzenesulfonate emerges by self-aggregation driven by hydrophobic interactions between the dodecylbenzene moiety and the hydrophobic first shell. The resulting double layer provides hydrophobic pockets suited for the intake of hydrophobic drugs. The nanoparticles were loaded with the anticancer drugs quercetin and 7-amino-4-methylcoumarin. Irradiation with X-rays was observed to release the potential anticancer drugs into the cytoplasm. In Michigan Cancer Foundation (MCF)-10 A cells, quercetin and 7-amino-4-methylcoumarin acted as antioxidants by protecting the non-tumorigenic cells from harmful radiation effects. In contrast, these agents increased the reactive oxygen species (ROS) formation in cancerous MCF-7 cells. Quercetin and 7-amino-4-methylcoumarin were shown to induce apoptosis via the mitochondrial pathway in cancer cells by determining an increase in TUNEL-positive cells and a decrease in mitochondrial membrane potential after irradiation. After X-ray irradiation, the survival fraction of MCF-7 cells with drug-loaded nanoparticles considerably decreased, which demonstrates the excellent performance of the double-layer stabilized nanoparticles as drug delivery vehicles.