Cisplatin-Cross-Linked DNA Origami Nanostructures for Drug Delivery Applications

Biocompatible DNA origami nanostructures (DONs) attract significant interest as potential targeted drug carriers. Their sensitivity to various environmental triggers is beneficial as a drug release or decomposition mechanism, but it also hinders their stability; therefore, they require some extent of cross-linking. Using cisplatin, we demonstrate that a molecule can both act as a therapeutic and cross-linking agent for DONs. In this work, triangular two-dimensional DONs are loaded with ∼1000 cisplatin molecules per nanostructure as confirmed by ICP-MS and STEM-EDS. Time dependence of the loading shows a saturation point and gradual cisplatin release. Above ∼1000 cisplatin molecules loaded per nanostructure, structural distortion occurs as analyzed by AFM and gel electrophoresis. Cross-linking persists even after thermal treatment of cisplatin-loaded DONs above typical DON denaturing temperatures preventing complete separation into DON components (scaffold and staples). Cisplatin-loaded DON cytotoxicity is tested on FaDu cells and compared to that of free cisplatin using MTT assays. Nanomolar quantities of cisplatin-loaded DONs reduce cell viability to 50% after 48–72 h. Considering the low dose required of cisplatin-loaded DONs to exhibit cytotoxic behavior and the known tumor-targeting properties of DONs, this system can be a promising drug carrier for cancer therapy worthy of further exploration.