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Light‐activatable minimally invasive ethyl cellulose ethanol ablation: Biodistribution and potential applications
Bioengineering & Translational Medicine ( IF 6.1 ) Pub Date : 2024-07-13 , DOI: 10.1002/btm2.10696
Jeffrey Yang 1, 2 , Chen‐Hua Ma 1 , John A. Quinlan 1, 3 , Kathryn McNaughton 1 , Taya Lee 1 , Peter Shin 1 , Tessa Hauser 1 , Michele L. Kaluzienski 1 , Shruti Vig 1 , Tri T. Quang 1 , Matthew F. Starost 4 , Huang‐Chiao Huang 1, 5 , Jenna L. Mueller 1, 5
Affiliation  

While surgical resection is a mainstay of cancer treatment, many tumors are unresectable due to stage, location, or comorbidities. Ablative therapies, which cause local destruction of tumors, are effective alternatives to surgical excision in several settings. Ethanol ablation is one such ablative treatment modality in which ethanol is directly injected into tumor nodules. Ethanol, however, tends to leak out of the tumor and into adjacent tissue structures, and its biodistribution is difficult to monitor in vivo. To address these challenges, this study presents a cutting‐edge technology known as Light‐Activatable Sustained‐Exposure Ethanol Injection Technology (LASEIT). LASEIT comprises a three‐part formulation: (1) ethanol, (2) benzoporphyrin derivative, which enables fluorescence‐based tracking of drug distribution and the potential application of photodynamic therapy, and (3) ethyl cellulose, which forms a gel upon injection into tissue to facilitate drug retention. In vitro drug release studies showed that ethyl cellulose slowed the rate of release in LASEIT by 7×. Injections in liver tissues demonstrated a 6× improvement in volume distribution when using LASEIT compared to controls. In vivo experiments in a mouse pancreatic cancer xenograft model showed LASEIT exhibited significantly stronger average radiant efficiency than controls and persisted in tumors for up to 7 days compared to controls, which only persisted for less than 24 h. In summary, this study introduced LASEIT as a novel technology that enabled real‐time fluorescence monitoring of drug distribution both ex vivo and in vivo. Further research exploring the efficacy of LASEIT is strongly warranted.

中文翻译:


光激活微创乙基纤维素乙醇消融:生物分布和潜在应用



虽然手术切除是癌症治疗的主要手段,但由于分期、位置或合并症,许多肿瘤无法切除。消融疗法可导致肿瘤局部破坏,在多种情况下是手术切除的有效替代方法。乙醇消融术就是这样一种消融治疗方式,其中乙醇直接注射到肿瘤结节中。然而,乙醇往往会从肿瘤中泄漏到邻近的组织结构中,并且其生物分布难以在体内监测。为了应对这些挑战,本研究提出了一种称为光激活持续曝光乙醇注射技术 (LASEIT) 的尖端技术。LASEIT 由三部分制剂组成:(1) 乙醇,(2) 苯并卟啉衍生物,能够基于荧光跟踪药物分布和光动力疗法的潜在应用,以及 (3) 乙基纤维素,在注射到组织中时形成凝胶以促进药物保留。体外药物释放研究表明,乙基纤维素使 LASEIT 中的释放速率减慢了 7×。与对照组相比,使用 LASEIT 时肝组织注射的体积分布改善了 6×。小鼠胰腺癌异种移植模型中的体内实验显示,LASEIT 表现出比对照组明显更强的平均辐射效率,并且与对照组相比,在肿瘤中持续长达 7 天,而对照组仅持续不到 24 小时。总之,本研究将 LASEIT 作为一种新技术引入,该技术能够对体外和体内的药物分布进行实时荧光监测。强烈需要进一步探索 LASEIT 的疗效。
更新日期:2024-07-13
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