*2.4. Atomic Force Microscopy (AFM)*

The morphology of OND and complexes was investigated by AFM imaging. AFM was performed on the Park NX20 (Park Systems, Suwon, South Korea) with tapping mode in the air, using PointProbe®Plus Non-Contact/Tapping Mode - High Resonance Frequency - Reflex Coating (known as PPP-NCHR) probes with a nominal tip radius of 7 nm. Samples deposited on freshly cleaved mica were used. For proper fixation of the nucleic acid, a divalent cation Mg2+ (10 mM) to electrostatically bridge the negatively charged surface of mica substrate to the anionic OND backbone was used [34,35]. Therefore, the mica was treated with 10-mM MgSO<sup>4</sup> for 5 min before the OND solution was applied. Ten microliters of 1-nM OND solution was allowed to attach for 5 min, rinsed with DI water and dried under nitrogen flow. Mica surface treatment was not necessary to absorb lipophilic complexes. The samples of the complexes were initially dissolved in chloroform and subsequently diluted in methanol. Ten microliters of 0.01-nM complex solution in methanol were spin-coated on fresh mica at 1000 rpm. Results were analyzed by SPIP (Image Metrology A/S, Hørsholm, Denmark) using the Particle and Pore analysis module, which enables height and volume analyses of the particles.
