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

0561805 - ÚFCH JH 2023 RIV US eng J - Journal Article
Sala, Leo Albert - Perečko, Tomáš - Mestek, O. - Pinkas, Dominik - Homola, T. - Kočišek, Jaroslav
Cisplatin-Cross-Linked DNA Origami Nanostructures for Drug Delivery Applications.
ACS Applied Nano Materials. Roč. 5, č. 9 (2022), s. 13267-13275. ISSN 2574-0970
R&D Projects: GA MŠMT(CZ) LM2018129; GA ČR GC20-04109J; GA MŠMT EF16_026/0008382
Grant - others:Ministerstvo školství, mládeže a tělovýchovy - GA MŠk(CZ) CZ.02.1.01/0.0/0.0/16_026/0008382
Institutional support: RVO:61388955 ; RVO:68081707 ; RVO:68378050
Keywords : atomic force microscopy * cisplatin * DNA nanotechnology * DNA origami * drug delivery * electron microscopy
OECD category: Physical chemistry; Physical chemistry (BFU-R); Cell biology (UMG-J)
Impact factor: 5.9, year: 2022
Method of publishing: Limited access
https://pubs.acs.org/doi/10.1021/acsanm.2c02976

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 similar to 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 similar to 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.
Permanent Link: https://hdl.handle.net/11104/0334305