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    Bioengineered Ionic Liquid for Catheter-Directed Tissue Ablation, Drug Delivery, and Embolization
    (Wiley-V C H Verlag Gmbh, 2024) Keum, Hyeongseop; Albadawi, Hassan; Zhang, Zefu; Graf, Erin; Dos Santos, Pedro Reck; Gunduz, Seyda; Oklu, Rahmi
    Delivery of therapeutics to solid tumors with high bioavailability remains a challenge and is likely the main contributor to the ineffectiveness of immunotherapy and chemotherapy. Here, a catheter-directed ionic liquid embolic (ILE) is bioengineered to achieve durable vascular embolization, uniform tissue ablation, and drug delivery in non-survival and survival porcine models of embolization, outperforming the clinically used embolic agents. To simulate the clinical scenario, rabbit VX2 orthotopic liver tumors are treated showing successful trans-arterial delivery of Nivolumab and effective tumor ablation. Furthermore, similar results are also observed in human ex vivo tumor tissue as well as significant susceptibility of highly resistant patient-derived bacteria is seen to ILE, suggesting that ILE can prevent abscess formation in embolized tissue. ILE represents a new class of liquid embolic agents that can treat tumors, improve the delivery of therapeutics, prevent infectious complications, and potentially increase chemo- and immunotherapy response in solid tumors.
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    Catheter-Directed Ionic Liquid Embolic Agent for Rapid Portal Vein Embolization, Segmentectomy, and Bile Duct Ablation
    (Wiley-V C H Verlag Gmbh, 2024) Cevik, Enes; Albadawi, Hassan; Zhang, Zefu; Demirlenk, Yusuf; Atar, Dila; Keum, Chris; Kim, Jinjoo
    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, is developed an ionic-liquid-based embolic material (LEAD) for portal vein embolization, liver ablation, and drug delivery. LEAD is optimized and characterized for diffusivity, X-ray visibility, and cytotoxicity. 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 is 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. Embolic materials currently used for PVE do not treat the tumor, risking tumor progression during the interval between PVE and surgery. Here, an ionic-liquid-based embolic material (LEAD) is developed that can embolize, ablate, and deliver therapeutics. With its 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. image