Progress toward Understanding the Interactions between DNA Nanostructures and the Cell

Abstract

Advances in DNA nanotechnology empower the programmable assembly of DNA building blocks (oligonucleotides and plasmids) into DNA nanostructures with precise architectural control. As DNA nanostructures are biocompatible and can naturally enter mammalian cells without the aid of transfection agents, they have found numerous biological or biomedical applications as delivery carriers of therapeutic and imaging cargoes into mammalian cells for at least a decade. Nevertheless, mechanistic studies on how DNA nanostructures interact with cells have remained limited and incomprehensive until 2–3 years ago. This Review presents the recent progress in elucidating the “cell–nano” interactions of DNA nanostructures, with an emphasis on three key classes of structures commonly utilized in intracellular applications: tile‐based structures, origami‐based structures, and nanoparticle‐templated structures. Structural parameters of DNA nanostructures and strategies of biochemical modification for promoting intracellular delivery are discussed. Biological mechanisms for cellular uptake, including specific pathways and receptors involved, are outlined. Routes of intracellular trafficking and degradation, together with strategies for re‐directing their trafficking, are delineated. This Review concludes with several aspects of the “bio–nano” interactions of DNA nanostructures that warrant future investigations.

Therapeutic siCCR2 Loaded by Tetrahedral Framework DNA Nanorobotics in Therapy for Intracranial Hemorrhage

“…In addition, some aptamers can be added to other vertices of the tFNA, enabling complex identification of specific proteins on the cytomembrane, thereby improving the specificity of targeting. [36] However, several in vivo studies have indicated that DNA nanostructures produced by origami methods [37] are easily denatured and digested in a physiological environment. [38] The tFNA nanorobotics also faces this problem because most tFNA, which have not been specially modified, are absorbed by the kidney and liver and then metabolically eliminated, after injection through the tail vein to reach the target organ.…”

Proteomic Exploration of Endocytosis of Framework Nucleic Acids

“…This strategy may be utilized as a generic approach to explore cellular processes of DNA nanostructures for biomedical applications, especially for small structures which are supposed to bind to protein domains favorably than large ones. [23] Furthermore, it may be applicable to other nanomaterials, such as liposomes and inorganic nanoparticles, [24] with caution for mass spectrometry measurements. [25] We envision this proteomic exploration strategy can provide a strong supplement for fluorescence tracing methods utilized in exploration of cellular process of nanomaterials.…”

Enabling Transgenic Plant Cell–Derived Biomedicines with Nanotechnology

“…In this perspective, we call for in‐depth studies on the interactions between NPs and plant cells, because rational design of NP‐based transformation tools warrants fundamental understanding in the cellular uptake of gene nanocarriers. [ 36 ]…”