Advancements in DNA nanotechnology for targeted drug delivery: Design strategies and applications

DNA nanotechnology has emerged as a promising strategy for designing drug delivery systems that are safe, non-immunogenic, biodegradable, non-toxic, and biocompatible. When employed as drug carriers, DNA nanostructures offer several advantages, including precise programmability, scalable synthesis under optimized conditions, high structural consistency, and customizable control over size, shape, and functionality. Their programmability arises from predictable Watson-Crick base pairing, enabling the rational design of complex nanostructures with superior precision compared to conventional synthetic nanoparticles or polymeric carriers. While large-scale DNA synthesis can be costly, advancements in enzymatic synthesis and high-throughput oligonucleotide production have demonstrated cost-reduction potential relative to certain polymeric or lipid-based nanocarriers. DNA nanostructures can enhance therapeutic efficacy, minimize cytotoxicity in healthy tissues, and improve the bioavailability of poorly soluble drugs. By conjugating them with functional elements—such as polymers, peptides, lipids, proteins, inorganic nanoparticles, and targeting ligands—via diverse bioconjugation strategies, their stability can be improved, circulation time extended, and targeted drug delivery efficiency optimized. Furthermore, smart DNA nanostructures equipped with targeting moieties or stimuli-responsive elements enable precise drug release, minimizing premature leakage and off-target effects. These advanced nanocarriers facilitate drug accumulation at target sites, enhance cellular uptake, bypass efflux mechanisms, and mitigate adverse reactions. By refining drug dispersion and release kinetics, they accelerate therapeutic action and improve overall treatment outcomes. This study explores the potential of DNA nanostructures in drug encapsulation and targeted delivery, highlighting their advantages over conventional nanocarrier systems.