Keum, Hyeongseop

AbstractTissue ablation techniques have emerged as a critical component of modern medical practice and biomedical research, offering versatile solutions for treating various diseases and disorders. Percutaneous ablation is minimally invasive and offers numerous advantages over traditional surgery, such as shorter recovery times, reduced hospital stays, and decreased healthcare costs. Intra‐procedural imaging during ablation also allows precise visualization of the treated tissue while minimizing injury to the surrounding normal tissues, reducing the risk of complications. Here, the mechanisms of tissue ablation and innovative energy delivery systems are explored, highlighting recent advancements that have reshaped the landscape of clinical practice. Current clinical challenges related to tissue ablation are also discussed, underlining unmet clinical needs for more advanced material‐based approaches to improve the delivery of energy and pharmacology‐based therapeutics.

AbstractEmbolic 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.

Abstract 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.