Shape-Dependent Self-Assembled Targeting Peptide Electrosensitizer for Enhanced Radiofrequency Ablation of Lipid-Rich Atherosclerotic Plaques.

Abstract

Radiofrequency ablation (RFA) is an effective strategy in realizing targeted lesions. However, its application for highly heterogeneous tissues like lipid-rich atherosclerotic plaques remains challenging due to its strong dependence on Joule heating. Current electrosensitizers used to enhance radiofrequency (RF) energy deposition are limited by their reliance on passive diffusion and random distribution. In this study, inspired by Geobacter OmcZ nanowire networks, electrosensitive atherosclerosis-targeting self-assembled peptides (EASPs) are designed as RF sensitizers to improve the heat deposition in lipid-rich plaques. Based on a targeting motif and a self-assembling module, EASPs accumulate in inflammatory regions of the aorta via recognition-induced self-assembly, resulting in in situ network aggregation. Taking advantage of the rapid amplification of nanofiber networks triggered by vascular cell adhesion molecule-1 and the unique shape-dependent electrical properties of the design, the local conductivity exhibits a rapid and sustained increase following systemic delivery, exceeding 2.39-fold the initial level within 2 h. EASP-assisted RFA demonstrates a significant enhancement in heat deposition, characterized by increased temperatures and expanded ablation zones in the diseased arteries. Notably, the 4 h accumulation group exhibited a 59.85% higher temperature increase and a 94.48% greater ablation area than the 2 h group. Through the integration of nanotechnology, this study provides a new approach to improving both the targeting precision and therapeutic efficiency of RFA-based atherosclerosis treatment.