Functionalizing DNA nanostructures for therapeutic applications

Abstract

Recent advances in nanotechnology have enabled rapid progress in many areas of biomedical research, including drug delivery, targeted therapies, imaging, and sensing. The emerging field of DNA nanotechnology, in which oligonucleotides are designed to self‐assemble into programmable 2D and 3D nanostructures, offers great promise for further advancements in biomedicine. DNA nanostructures present highly addressable and functionally diverse platforms for biological applications due to their ease of construction, controllable architecture and size/shape, and multiple avenues for chemical modification. Both supramolecular and covalent modification with small molecules and polymers have been shown to expand or enhance the functions of DNA nanostructures in biological contexts. These alterations include the addition of small molecule, protein, or nucleic acid moieties that enable structural stability under physiological conditions, more efficient cellular uptake and targeting, delivery of various molecular cargos, stimulus‐responsive behaviors, or modulation of a host immune response. Herein, various types of DNA nanostructure modifications and their functional consequences are examined, followed by a brief discussion of the future opportunities for functionalized DNA nanostructures as well as the barriers that must be overcome before their translational use. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Emerging Technologies Biology‐Inspired Nanomaterials > Nucleic Acid‐Based Structures

Radiolabeling and Preliminary Evaluation of 99mTc-Labeled DNA Cube Nanoparticles as Potential Tracers for SPECT Imaging

“…In this field, DNAs are used as non-biological nanomaterials, rather than as genetic information carriers for living cells. DNA nanostructures, which can be functionalized with different targeting ligands (such as organic molecules, peptides, antibody, aptamer and so on), 9 display excellent delivery capacity for various drugs (such as CpG, doxorubicin, or siRNA), as well as signal moieties (fluorescent dyes or radionuclides). These signal molecules can be utilized to explore the in-vivo information of DNA nanostructures including biodistribution, metabolism and stability properties.…”

What’s Next after Lipid Nanoparticles? A Perspective on Enablers of Nucleic Acid Therapeutics

“…Exploring the base pair complementarity driven self-assembly to create nucleic acid based nanosystems for delivery is another interesting direction in this area. DNA nanotechnology has been exploited to develop delivery vehicles where DNA self-assembles through the Watson–Crick base pairing. , The potential for this platform arises from their (i) well-defined shape and easily tunable size with monodispersity, (ii) biocompatibility, (iii) convenient functionalization with desired chemical conjugations, and (iv) programmability to introduce stimuli-responsive release of cargo. − This technology has been explored for intracellular drugs , and protein delivery and has the potential to be extended to nucleic acids. For example, a self-assembled DNA tetrahedral nanostructure was reported for siRNA delivery, which showed effective gene silencing in vivo in a nude mouse bearing a KB xenograft tumor .…”

Advances in the use of nanomaterials for nucleic acid detection in point-of-care testing devices: A review

“…Interestingly, the limit of detection of a clinic sample is 3 fM, and only requires a simple dark-field microscope, which shows that the assay has high simplicity and sensitivity. A DNA nanostructure is a technique for artificially designing and producing useful NA structures, which, as a bridge, connect the relationship between optoelectronics, thermology dynamics, and genetic information (Zhang et al, 2020;Henry and Stephanopoulos, 2021;Qin et al, 2022). Although not active, a DNA nanostructure has these advantages: low toxicity, high resistance to degradation in biological media, and an ideal ability to enter cells without transfection agents.…”