Sprecher
Beschreibung
DNA nanostructures can be made by combining a long single-strand DNA scaffold with more than 200 short DNA oligonucleotides (staples) that will direct the folding of the scaffold to any pre-designed shape [1]. DNA nanostructure products have numerous functions, such as studying nanoscale biological interactions and facilitating drug delivery. It has been shown that DNA nanostructures can bind platelet membranes without triggering activation [2], however, DNA nanostructures have not been explored for their potential to target activated platelets and deliver thrombolytics. In this project, we investigate the interaction of various DNA nanostructures with activated platelets, and we assess their potential for anticoagulant drug delivery. DNA nanostructures with different shapes (triangle, tetrahedron, 5-well-frame) were synthesized and visualized using atomic force microscopy (AFM) and transmission electron microscopy (TEM). Flow cytometry reveals that 1 nM folded DNA nanostructures (triangular, tetrahedral, and 5-well-frame structures) specifically bind to activated platelets with high affinity in 30 minutes of incubation time, without modifications. Confocal microscopy images suggest the internalization of these structures into activated platelets, where they gather in the cell center. Future work will focus on conjugating thrombolytic agents to DNA nanostructures and evaluating their effects on platelet function and clot dissolution. Peptides will also be attached onto the nanostructures for higher affinity and tuning of the binding. This study highlights the potential of DNA nanotechnology in developing targeted anticoagulant therapies for thrombotic diseases.
References
1. Rothemund, P. W. K. Folding DNA to create nanoscale shapes and patterns. Nature 440, 297–302 (2006).
2. Roka-Moiia, Y. et al. DNA Origami–Platelet Adducts: Nanoconstruct Binding without Platelet Activation. Bioconjugate Chem. 33, 1295–1310 (2022).
