Tumor casting hydrogels for interventional radiology treatment of hepatocellular carcinoma

项目摘要 肝细胞癌（HCC）是美国癌症相关死亡上升最快的原因。之一 用于HCC的主要治疗方法是栓塞，即用栓塞剂阻断供给肿瘤的血管。 微珠药物洗脱珠（DEB）经常用于此目的。尽管开发了 DEB，患者5年生存率仅为27%。这可能是由于药物洗脱特性差， 不完全栓塞，因为与肿瘤毛细血管的尺寸相比，珠粒较大。与此同时， 由于通常是放射性的，这些珠子不能通过成像可视化，因此评估它们的放射性是具有挑战性的。 手术期间成功展开。因此，开发可生物降解的材料， 阻塞血管，具有可调的药物释放，以及包含具有不透射线特性的材料， 将是有利的。我们提出了一种新的注射，热敏，不透射线和药物洗脱 水凝胶作为HCC治疗的治疗平台，其将完全闭塞肿瘤血管。 肾可清除金纳米颗粒（AuNP）将用于使凝胶不透射线，因为它们具有强的 X射线衰减，生物相容性极佳，最终可排出体外。在这项研究中， 将合成AuNP/载药水凝胶，并对其进行物理和化学表征。体内 研究检查凝胶的造影剂生成特性、其抗肿瘤作用、其生物分布和 将进行清理。这项工作的结果将为额外的有效性和安全性奠定基础 在临床翻译之前需要进行研究。

PROJECT SUMMARY Hepatocellular carcinoma (HCC) is the fastest rising cause of cancer-related death in the United States. One of the major treatments used for HCC is embolization, i.e. blocking the blood vessels feeding a tumor with microbeads. Drug-eluting beads (DEBs) are frequently used for this purpose. Despite the development of DEBs, patient survival rate is only 27% at 5 years. This may be due to poor drug eluting characteristics and incomplete embolization since the beads are large compared to the size of tumor capillaries. At the same time, being typically radiolucent, those beads cannot be visualized via imaging, so it is challenging to assess their successful deployment during the procedure. Therefore, the development of biodegradable materials that can block blood vessels, have tunable drug release, as well as incorporate materials with radiopaque properties, would be advantageous. We propose a novel injectable, thermo-sensitive, radiopaque and drug-eluting hydrogel as a therapeutic platform for HCC treatment, which will completely occlude tumor blood vessels. Renally clearable gold nanoparticles (AuNP) will be used to render the gel radiopaque since they have strong X-ray attenuation, excellent biocompatibility and can eventually be excreted. In this proposed research, AuNP/drug loaded hydrogels will be synthesized and will be physically and chemically characterized. In vivo studies examining the contrast generating properties of the gel, its anti-tumor effects, its biodistribution and clearance will be performed. The results of this work will set the stage for the additional efficacy and safety studies needed prior to clinical translation.