Magnetic Nanocomposites for Catheter-Directed Drug Delivery to Liver Tumors

项目总结 6-甲氧乙基氨基甲烷(Mean)是一种新型的抗癌新药，对癌症有很强的疗效。 肝细胞癌的治疗。然而，即使卑鄙的提议大大减少了系统性 毒性与上一代氨甲酰胺相比，全身给药仍可能导致潜在的严重 不良事件。先前开发的用于治疗肝癌的导管引导技术包括 Y-90微球放射栓塞术或药物洗脱微球选择性灌注化疗栓塞术 肿瘤血管床。对于这些方法，局部给药可显著降低全身毒性。 这是由于选择性导尿管给药。提出了均值洗脱磁的发展方向。 由可生物降解的USPIO纳米团簇嵌入的纳米复合材料(Mean-MNC) 聚合物基质，允许受控药物释放和选择性经导管给药至肝细胞癌。这些 纳米复合给药平台提供了显著提高Mean对 治疗肝癌，同时通过导管定向输送减少全身暴露。通过协作 基于我们在材料科学、纳米技术、生物医学工程和 介入肿瘤学，我们寻求开发一种强有力的新方法，用于图像引导的导管定向输送 对肝脏肿瘤来说是不公平的。这一临床前项目将在一只成熟的大鼠身上解决以下具体目标 肝癌模型： 目的1：确定微流控Mean-MNC合成方案与合成结果的关系 加载、释放动力学和磁共振成像(MRI)特性。 目的：比较a)经导管输注MNCs和静脉注射MNCs后的肿瘤反应。 Mean和b)MNC对诱发反应的Mean-MNC传递的MRI测量。

PROJECT SUMMARY 6-methoxyethylamino numonafide (MEAN) is an innovative new anti-cancer drug with potent efficacy for the treatment of hepatocellular carcinoma (HCC). However, even though MEAN offers to importantly reduce systemic toxicity compared to prior generation amonafides, systemic administration may still lead to potentially serious adverse events. Previously developed catheter-directed techniques for treatment of HCC include radioembolization with Y-90 microspheres or chemoembolization with drug-eluting beads selectively infused into the tumor vascular beds. For these approaches, local delivery affords significant reductions in systemic toxicity due to selective catheter-directed delivery. We propose the development of MEAN-eluting magnetic nanocomposites (MEAN-MNCs) consisting of embedded porous USPIO nano-clusters in a biodegradable polymer matrix to permit controlled drug release and selective transcatheter delivery to HCC. These nanocomposite drug delivery platforms offer the potential to significantly increase the efficacy of MEAN for the treatment of HCC while reducing systemic exposures via catheter-directed delivery. Through a collaborative project building upon our strengths in materials science, nanotechnology, biomedical engineering and interventional oncology, we seek to develop a powerful new approach for image-guided catheter-directed delivery of MEAN to liver tumors. This pre-clinical project will address the following Specific Aims in a well-established rat model of liver cancer: Aim 1: To determine the relationship between micro-fluidic MEAN-MNC synthesis protocols and resulting MEAN loading, release kinetics, and magnetic resonance imaging (MRI) properties. Aim 2: To compare a) tumor responses following transcatheter infusion of MEAN-MNCs and IV administration of MEAN and b) MRI measurements of MEAN-MNC delivery to the elicited response.