Intercalation of Bioactive Molecules into Nanosized ZnAl Hydrotalcites for Combined Chemo and Photo Cancer Treatment

Hydrotalcites-like compounds, also known as anionic clays or layered double hydroxides, represent the only example of lamellar solid with positively charged layers and exchangeable interlayer anions. In this study, a nanostructured HTlc with formula [Zn0.72Al0.28(OH)2] Br0.28·0.69 H2O was used as inorganic drug delivery system for anticancer therapy. Two different molecules were selected for being separately intercalated into ZnAl-HTlc: the anticancer drug norcantharidin, known for inducing cell cycle arrest at G2/M phase, and the tetra-sulfonated aluminum phthalocyanine, a photosensitizer used in anticancer photodynamic therapy. The obtained hybrid ZnAl-HTlc, were characterized in terms of X-ray powder diffraction pattern, thermogravimetric analysis, scanning electron microscopy, drug release profile, in vitro cytotoxicity, and ability to produce ROS and 1O2 upon light irradiation. Our results clearly indicate that the two selected compounds are efficiently intercalated within HTlc layers. Moreover, in vitro preliminary studies on a panel of cancer cells lines account for a greater cytotoxicity of the two drugs once loaded on HTlc either when administrated singularly or in combination. In addition, the analysis of the synergistic effect of the two formulations was evaluated by determining their combination index, which showed a greater cytotoxicity when using as a 1:2 ratio of AlPcS4@HTlc and NCTD@HTlc, respectively.