DNA Framework-Enabled Three Dimensional Organization of Antiarrhythmic Drugs for Radiofrequency Catheter Ablation.

Pre-organizing molecular drug within a microenvironment is crucial for the development of efficient and controllable therapeutic systems. Here, we report the use of tetrahedral DNA framework (TDF) to pre-organize antiarrhythmic drugs (herein doxorubicin, Dox) in three dimensions for catheter ablation, a minimally invasive treatment for fast heartbeats, aiming to address potential complications linked to collateral tissue damage and the post-ablation AF recurrence resulting from incomplete ablation. Dox pre-organization within TDF transforms its random distribution into a confined, regular spatial arrangement governed by DNA. This, combined with the high affinity between Dox and DNA, significantly increases local Dox concentration. The exceptional capacity of TDF for cellular internalization leads to a 5.5-fold increase in intracellular Dox amount within cardiomyocytes, effectively promoting cellular apoptosis. In vivo investigations demonstrate that administering TDF-Dox reduce the recurrence rate of electrical conduction after radiofrequency catheter ablation (RFCA) to 37.5%, compared with the 77.8% recurrence rate in the free Dox-treated group. Notably, the employed Dox dosage exhibits negligible adverse effects in vivo. This study presents a promising treatment paradigm that strengthens the efficacy of catheter ablation and opens a new avenue for reconciling the paradox of ablation efficacy and collateral damage. This article is protected by copyright. All rights reserved.