Cisplatin-Cross-Linked DNA Origami Nanostructures for Drug Delivery Applications
Leo Sala, Tomáš Perečko, Oto Mestek, Dominik Pinkas, Tomáš Homola, Jaroslav Kočišek
Abstract
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.