Facile synthesis of platinated DNA nanoparticles with radiosensitizing potential

Abstract

DNA nanostructures are promising drug delivery platforms but often suffer from limited structural stability and high production complexity. Cisplatin can cross-link DNA and act as a therapeutic agent, offering a simplified approach to stabilize DNA nanostructures while incorporating therapeutic functionality. Here, we explore cisplatin-mediated compaction of a single-stranded DNA scaffold to form stable nanoparticles and evaluate their potential as radiosensitizers. Cisplatin-induced cross-linking produced compact DNA nanoparticles with size and morphology controlled by mixing ratio and incubation time, reaching maximum loading near a 1:1 cisplatin-to-nucleotide mixing ratio, resulting in 0.28 ± 0.06 bound Pt atoms per nucleotide. The nanoparticles showed high thermal stability with the onset of thermal degradation between 80 and 90 °C and remained structurally stable at 4 °C storage for months. Clonogenic assays in FaDu cells demonstrated radiosensitization, with a dose enhancement ratio of 1.17 ± 0.07 at 10% survival. Cisplatin-mediated cross-linking provides a simple and effective method for producing stable DNA nanoparticles without complex origami assembly. The resulting structures retain the radiosensitizing properties of platinum while offering improved stability and storage characteristics. These platinated DNA nanoparticles represent a promising platform for further development of scalable DNA-based radiosensitizers with high drug loading, monodispersity, stability, and versatility for further functionalization.