Advances in regenerative medicine applications of tetrahedral framework nucleic acid-based nanomaterials: an expert consensus recommendation

Abstract

With the emergence of DNA nanotechnology in the 1980s, self-assembled DNA nanostructures have attracted considerable attention worldwide due to their inherent biocompatibility, unsurpassed programmability, and versatile functions. Especially promising nanostructures are tetrahedral framework nucleic acids (tFNAs), first proposed by Turberfield with the use of a one-step annealing approach. Benefiting from their various merits, such as simple synthesis, high reproducibility, structural stability, cellular internalization, tissue permeability, and editable functionality, tFNAs have been widely applied in the biomedical field as three-dimensional DNA nanomaterials. Surprisingly, tFNAs exhibit positive effects on cellular biological behaviors and tissue regeneration, which may be used to treat inflammatory and degenerative diseases. According to their intended application and carrying capacity, tFNAs could carry functional nucleic acids or therapeutic molecules through extended sequences, sticky-end hybridization, intercalation, and encapsulation based on the Watson and Crick principle. Additionally, dynamic tFNAs also have potential applications in controlled and targeted therapies. This review summarized the latest progress in pure/modified/dynamic tFNAs and demonstrated their regenerative medicine applications. These applications include promoting the regeneration of the bone, cartilage, nerve, skin, vasculature, or muscle and treating diseases such as bone defects, neurological disorders, joint-related inflammatory diseases, periodontitis, and immune diseases.

Tetrahedral Framework Nuclear Acids Can Regulate Interleukin-17 Pathway to Alleviate Inflammation and Inhibit Heterotopic Ossification in Ankylosing Spondylitis

“…Tetrahedral frame nucleic acids (tFNAs) are bioactive nanomaterial with tetrahedron-like structures that have been widely studied in the biomedical field. − Its editability allows it to carry coding sequence in a framework structure for the treatment of specific diseases. The small size and the negative surface potential of tFNAs determine that it could be quickly ingested by cells to exert various biological effects.…”

From tensegrity to human organs-on-chips: implications for mechanobiology and mechanotherapeutics

“…New materials being explored for medical applications also leverage DNA nanotechnologies that rely on molecular self assembly methodologies, such as DNA Origami, to fabricate structures with programmable material properties and 3D structures on the nanometer scale [ 77 , 78 ]. These structures can be modified in precise manners to display biomolecular cues (e.g.…”

DNA-Based Nanomaterials as Drug Delivery Platforms for Increasing the Effect of Drugs in Tumors

“…The TDNs are basically 7 to 20 nm in diameter [ 151 ]. By adjusting its orientation, TDN, in contrast to other DNA nanostructures, reduces electrostatic repulsive interactions and redistributes the TDNs’ uneven charge at the membrane surface, allowing it to actively penetrate the cell membrane using the vertex [ 252 ]. Tetrahedrons may be taken up through caveolin-dependent receptor-mediated endocytosis, according to a theory put out by Liang and colleagues.…”

“…The receptor(s) in this uptake are not exactly established [ 5 ]. TDNs are carried into lysosomes by microtubules in a highly organized manner after entering a cell through membrane caveolin, preserving structural stability in the cell cytoplasm for up to 12 h [ 252 ]. While TDNs maintain their structural stability within cells for a relatively long time, their location in lysosomes prevented them from being used as efficient delivery systems.…”