Wireframe DNA Origami for the Cellular Delivery of Platinum(II)-Based Drugs

Abstract

The DNA origami method has revolutionized the field of DNA nanotechnology since its introduction. These nanostructures, with their customizable shape and size, addressability, nontoxicity, and capacity to carry bioactive molecules, are promising vehicles for therapeutic delivery. Different approaches have been developed for manipulating and folding DNA origami, resulting in compact lattice-based and wireframe designs. Platinum-based complexes, such as cisplatin and phenanthriplatin, have gained attention for their potential in cancer and antiviral treatments. Phenanthriplatin, in particular, has shown significant antitumor properties by binding to DNA at a single site and inhibiting transcription. The present work aims to study wireframe DNA origami nanostructures as possible carriers for platinum compounds in cancer therapy, employing both cisplatin and phenanthriplatin as model compounds. This research explores the assembly, platinum loading capacity, stability, and modulation of cytotoxicity in cancer cell lines. The findings indicate that nanomolar quantities of the ball-like origami nanostructure, obtained in the presence of phenanthriplatin and therefore loaded with that specific drug, reduced cell viability in MCF-7 (cisplatin-resistant breast adenocarcinoma cell line) to 33%, while being ineffective on the other tested cancer cell lines. The overall results provide valuable insights into using wireframe DNA origami as a highly stable possible carrier of Pt species for very long time-release purposes.

Design and Assembly of a Cargo-agnostic Hollow Two-lidded DNA Origami Box for Drug Delivery

“…These have been used to deliver or release drugs or model molecules including doxorubicin, platinum-based molecules, and antibody fragments to name a few. 8,10,12,[24][25][26] Molecules have been attached to the surface of the DNA origami structure through electrostatic interactions as well as through covalent linkages. For instance, doxorubicin and similar molecules have been bound electrostatically to the surface of a 2D DNA surface.…”

“…Other DNA origami designs show hollow tubes or wireframe structures that can gradually release drug when delivered, but the release is uncontrolled due to the open cage designs. 2,3,12,25 Another design is a DNA origami tube lacking lids that can be opened along its length based on logic nucleic acid keys (similar to what was mentioned above). Each of these tube designs still suffer from non-specific delivery due to open-ended or wireframe designs.…”

“…Each of these tube designs still suffer from non-specific delivery due to open-ended or wireframe designs. 2,3,8,25 Enclosed 3D DNA origami structures have been designed with pH responsive lids. 30 However, the loading potential is minimal in this design due to edges that are multiple helices thick, resulting in a small internal volume.…”