Carbon dots (CDs) are nanoscale carbon materials with tunable optical properties, low toxicity, and modular functionalization, making them a promising material for biomedical applications. For safe and efficient applications in theranostics, it is essential to assess how CDs interact with biomolecules. Here, we focus on the effect of CDs on the structure and function of nucleic acids (NAs), relevant to NA structural stability, chromatin organization, and gene regulation. We performed more than 150 μs of atomistic molecular dynamics simulations, encompassing a diverse set of NA structures, from canonical DNA and RNA helices through noncanonical motifs such as tetraloops and G-quadruplexes, up to nucleosomes. We simulated their interactions with graphitic CDs with two sizes and distinct surface chemistries: neutral hydrophobic (CD0), negatively charged (CD-), and positively charged (CD+). We identified multiple nonspecific interaction modes including stacking to bases, CH-π contacts, and electrostatic interactions with the NA backbone. All CD types formed contacts with NAs, but only CD+ remained tightly bound and is therefore relevant for NA-related applications. The CD nonspecific binding did not compromise the global NA architecture, and we did not observe any intercalation or base-pair disruption. In the nucleosome, CD+ adsorb to DNA and occasionally bridge adjacent DNA gyres, that may alter local chromatin dynamics. In summary, the surface charge and particle size emerged as the key determinants of NA-CD interactions, providing atomistic guidance for the rational design of CDs optimized for theranostic applications.

Department of Physical Chemistry Faculty of Science Palacký University Olomouc 17 listopadu 12 771 46 Olomouc Czech Republic

Faculty of Electrical Engineering and Computer ScienceVŠB Technical University of Ostrava 17 listopadu 2172 15 708 00 Ostrava Poruba Czech Republic

Institute of Biophysics of the Czech Academy of Sciences Královopolská 135 612 00 Brno Czech Republic

IT4Innovations VŠB Technical University of Ostrava 17 listopadu 2172 15 708 00 Ostrava Poruba Czech Republic

Regional Center of Advanced Technologies and Materials Czech Advanced Technology and Research Institute Palacký University Olomouc Šlechtitelů 27 779 00 Olomouc Czech Republic

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