Enhanced Targeted Therapeutics: Investigating DNA Coverage Density Effects on the Structural Dynamics of DNA-Functionalized Gold Nanoparticles for Precision Nanomedicine

The functionalization of gold nanoparticles (AuNPs) with DNA represents a major advance in nanomedicine, offering new opportunities to improve the specificity, efficiency, and controllability of diagnostic and therapeutic systems. This approach combines the distinctive physicochemical, optical, and surface properties of AuNPs with the molecular recognition capabilities, structural programmability, and biological relevance of DNA. Consequently, DNA-functionalized AuNPs can be engineered as hybrid nanostructures that interact selectively with biological targets and respond to specific molecular environments. In this study, the design, structural organization, and behavior of DNA-modified AuNPs are investigated through a complementary combination of molecular simulations and experimental approaches. Particular attention is devoted to the influence of DNA surface coverage on chain conformation, intermolecular interactions, spatial distribution, and packing efficiency at the nanoparticle interface. The results indicate that variations in DNA grafting density can promote favorable conformational rearrangements and lead to a more organized and stable nucleic acid shell. These changes may affect target accessibility, hybridization efficiency, colloidal stability, and the overall biological performance of the resulting nanoconjugates. By clarifying the relationship between surface composition and DNA organization, this work provides a deeper understanding of the structural principles governing DNA–AuNP assemblies. Such knowledge may facilitate the rational design of nanoscale platforms for targeted gene delivery, controlled gene regulation, molecular diagnostics, biosensing, and precision treatment strategies. Overall, the findings highlight the versatility of DNA-functionalized AuNPs and support their continued development as adaptable tools for personalized medicine, targeted therapeutics, and the diagnosis and treatment of complex diseases.