Metal ion (Mn+)-condensed DNA nanoparticles: Synthesis, properties, and applications

Metal ion (Mⁿ⁺)-induced DNA condensation is a critical process observed in both natural and synthetic contexts, playing a central role in the formation of nanoscale DNA-based materials. This phenomenon leverages the ability of multivalent Mⁿ⁺s to neutralize the negatively charged DNA phosphate backbone, promote electrostatic cross-linking, and enable coordination bonding, leading to compact and organized DNA nanostructures. Recent advancements have focused on synthesizing Mⁿ⁺-condensed DNA nanoparticles (Mⁿ⁺-CDNPs) through controlled molecular assembly, utilizing the interplay of DNA sequence specificity, Mⁿ⁺ type, and environmental conditions. The choice of Mⁿ⁺ significantly influences the properties of Mⁿ⁺-CDNPs, imparting functionalities including fluorescence, magnetism, and catalytic activity, which are tailored for applications in biosensing, diagnostics, and therapeutic delivery. However, several challenges remain in fully realizing the potential of Mⁿ⁺-CDNPs. These include scalability issues, morphological control beyond isotropic spherical nanoparticles, and ensuring biocompatibility, particularly when using heavy Mⁿ⁺s. Innovations in synthesis strategies, such as optimizing phase transitions during condensation and incorporating programmable DNA sequences, have enabled enhanced structural precision and functionality. Surface modification techniques, such as coating with metal–organic frameworks (MOFs) or silica shells, have further expanded the stability and applicability of Mⁿ⁺-CDNPs. Additionally, the inclusion of functional additives, such as drugs and proteins, has broadened their use in targeted therapy and controlled release systems. This review highlights the advances in the synthesis, properties, and applications of Mⁿ⁺-CDNPs, emphasizing their potential as multifunctional platforms for biomedical and nanotechnological innovations. Future efforts must address challenges in reproducibility, toxicity, and structural diversity through interdisciplinary approaches combining experimental, computational, and engineering strategies. By overcoming these barriers, Mⁿ⁺-CDNPs hold promise for transformative advancements in nanomedicine, chemical sensing, and programmable material design.