Catheter‐Directed Ionic Liquid Embolic Agent for Rapid Portal Vein Embolization, Segmentectomy, and Bile Duct Ablation

Abstract

Embolic materials currently in use for portal vein embolization (PVE) do not treat the tumor, which poses a risk for tumor progression during the interval between PVE and surgical resection. Here, we developed an ionic‐liquid‐based embolic material (LEAD) for portal vein embolization. After synthesizing and evaluating ionic liquids (ILs) at different molar ratios, IL3:1 emerged as the optimal candidate based on its superior diffusion of solubilized chemotherapy drugs and near‐infrared drug surrogates through tissue‐like matrices, alongside significant cytotoxicity against cholangiocarcinoma and hepatocellular carcinoma cells, proving its suitability for the LEAD formulation. LEAD was further optimized and characterized for diffusivity, X‐ray visibility, and cytotoxicity for in vivo use. In the porcine renal embolization model, LEAD delivered from the main renal artery reached vasculature down to 10 microns with uniform tissue ablation and delivery of small and large therapeutics. In non‐survival and survival porcine experiments, successful PVE was achieved in minutes, leading to the expected chemical segmentectomy, and delivery of a large protein drug (i.e., Nivolumab) with LEAD. In cholangiocarcinoma mouse tumor models and in ex vivo human tumors, LEAD consistently achieved an effective ablation and wide drug distribution. Furthermore, various strains of drug‐resistant patient‐derived bacteria showed significant susceptibility to LEAD, suggesting that LEAD may also prevent infectious complications resulting from tissue ablation. With its capabilities to embolize, ablate, and deliver therapeutics, ease of use, and a high safety profile demonstrated in animal studies, LEAD offers a potential alternative to tumor ablation with or without PVE for FLR growth.This article is protected by copyright. All rights reserved