Introduction: Although drug delivery systems, such as liposomes, the cationic polymer, and carbon nanotubes, exist, few materials can be applied in the clinic. In recent years, the use of DNA nanostructures as a tool for drug delivery has been considered. In this review, the applications of DNA nanoparticles in drug delivery are described. Then we discuss existing challenges that may limit the clinical applications of DNA nanoparticles.
Methods: successful drug delivery: Since the current cancer treatment drugs are not capable of distinguishing between cancer cells and normal cells, DNA nanoparticles are designed in a specific manner that they can target only cancer cells. In one study, DNA–affibody nanoparticle containing doxorubicin was prepared for the treatment of BT474 cells (cells with overexpression of HER2). Also, they used only doxorubicin as a control to compare its activity with that of the nanoparticle. Since the affibody binds specifically to the HER2 receptor, the DNA–affibody–drug nanoparticle showed a greater binding ability to HER2 overexpressing BT474 cells compared to doxorubicin itself. Also, studies reveal that DNA tetrahedron can be a good candidate to overcome MDR in cancer cells. The results of one study demonstrated that combining doxorubicin and DNA tetrahedron is considerably cytotoxic to multidrug-resistant breast cancer cells (MCF- 7/ADR), whereas free doxorubicin is virtually non-cytotoxic for cancer cells.
challenges and possible solution: 1) Stability: Studies show that binding to the protein such as human serum albumin (HAS) significantly reduced the degradation of DNA strands. The serum half-life of these DNA nanostructure-HSA complexes reaches up to 22 hours, whereas unconjugated DNA strands are degraded within minutes. In another study, the effect of DNA structural changes on the stability of nanoparticles was investigated. For example, DNA nanostructures synthesis using L- deoxyribose instead of D-deoxyribose enhances the cellular uptake and serum stability. 2) cellular uptake: It is very important to design approaches for selective uptake of DNA nanostructures by specific tissues and cells. The surfaces of DNA nanostructures are fully addressable, allowing for the incorporation of multiple ligands (such as antibodies, aptamers, or receptors). For example, the sgc8 aptamer, which can bind to the human protein tyrosine kinase 7 (PTK7) on the surface of T cells, was used to direct drug-loaded nanotrains to human T-cell acute lymphocytic leukemia.
3) biosafety: DNA outside the eukaryotic nucleus is recognized as a foreign molecule by the immune system. In nature, encapsulation of the genome and capsid by the lipid membrane is a viral strategy to protect the immune system. Inspired by viral particles, Perrault and Shih designed their DNA nano-octahedron with a PEGylated lipid bilayer around it. The results show that the encapsulation leads to protection against DNase I digestion, reduces stimulatory cytokine production and evades uptake by splenocytes. In contrast, non-enveloped DNA activates a potent immune response and displays rapid degradation after injection.
Results: Use of DNA nanostructures for drug delivery compared to other available vectors
has advantages, including: 1) Biocompatibility 2) predictable intermolecular interactions (Watson−Crick base pairing) 3) Easy design and synthesis 4) capable of binding to different molecules (such as antibodies, or aptamers) for smart drug delivery. Despite these advantages, the use of DNA nanostructures in biomedicine has limitations such as low serum stability, cellular uptake, biosafety, and high costs. Various studies have been conducted to address these challenges and efforts are ongoing.
Conclusion: Despite the challenges, the application of DNA nanostructures for controllable drug release showed great potential in smart drug delivery. Due to their unique properties, we predict that DNA nanostructures will become powerful agents for drug delivery, especially in the treatment of cancers and other related diseases.
Keywords: DNA nanostructures, drug delivery, Opportunities and challenges