ROS-induced SPIO Targeted Platform for Transarterial Liver Cancer Therapy

ROS诱导的SPIO靶向平台用于经动脉肝癌治疗

• 批准号: 10310481
• 负责人: Khashayar Farsad
• 金额: $ 21.17万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10310481
• 关键词: 90Y; Antineoplastic Agents; Apoptosis; Arteries; Autophagocytosis; Blood Glucose; Catheters; Cell Death; Cell Proliferation; Cessation of life; Chelating Agents; Chemoembolization; Clinical; Consumption; Cytotoxic Chemotherapy; Cytotoxin; Data; Diagnosis; Disease; Drug Kinetics; Effectiveness; Enzymes; Evaluation; FDA approved; Future; Generations; Glucose; Hepatic artery; Hydrogen Peroxide; In Vitro; Liver neoplasms; Malignant Neoplasms; Malignant neoplasm of liver; Metabolic; Metabolism; Modeling; Modification; Molecular; Monitor; Necrosis; Neoplasms in Vascular Tissue; Oxides; PUVA Photochemotherapy; Positron-Emission Tomography; Primary carcinoma of the liver cells; Radiation therapy; Radioembolization; Radiolabeled; Radionuclide therapy; Rattus; Reaction; Reactive Oxygen Species; Recurrence; Reporting; Safety; Science; Serum; Surface; Technology; Testing; Therapeutic; Therapeutic Embolization; Therapeutic Index; Thinness; Toxic effect; Tube; Unresectable; anti-cancer; base; cancer cell; cancer therapy; catalyst; chemotherapy; clinical translation; cyanine dye 5; enzyme therapy; fast protein liquid chromatography; feeding; flexibility; glucose oxidase; hepatocellular carcinoma cell line; image guided; improved; in vivo; in vivo evaluation; innovation; intravenous administration; iron oxide; iron oxide nanoparticle; liver cancer model; molecular imaging; nanotechnology platform; nanotherapy; neoplastic cell; novel; oxidative damage; response; spatiotemporal; standard of care; synergism; systemic toxicity; targeted delivery; theranostics; tumor; uptake; zeta potential

Title: SPIO-GOx conjugate for transarterial liver cancer therapy Abstract: Hepatocellular carcinoma (HCC) is the sixth most common malignancy worldwide and ranks third amongst cancer-related deaths, with over 700,000 new cases diagnosed each year. Improved therapies for this disease is urgently needed. Cancer cells die in three ways: apoptosis, necrosis and autophagy. A significant increase in intracellular reactive oxygen species (ROS) can cause irreversible oxidative damage, leading to cell death through both apoptosis and necrosis. Recently, our team created a novel SPIO-GOx nanoplatform, synergizing ROS and metabolic depletion therapies. Using in vitro and in vivo studies, we found this nanoplatform could produce very high levels of ROS and highly efficient tumor cell destruction. Maximizing the therapeutic profile of this agent through targeted delivery and minimal systemic toxicity will be crucial for effective clinical translation. Transarterial chemoembolization (TACE), where chemotherapy is delivered directly into tumor-feeding arteries, is the current standard of care for unresectable HCC. TACE synergizes delivery of chemotherapy with embolization of tumor blood vessels while significantly minimizing toxicity due to targeted delivery. In this project, we plan to leverage our innovative SPIO-GOx theranostic nanoplatform with trans-arterial delivery technology to investigate the potential application in liver cancer treatment. If successful, we may advance the science of liver cancer treatment using this novel theranostic nanotherapy.

标题：SPIO-GOx结合物用于经动脉肝癌治疗 摘要： 肝细胞癌（HCC）是世界范围内第六大常见恶性肿瘤， 在癌症相关死亡中排名第三，每年诊断出超过70万例新病例。 因此，迫切需要改进这种疾病的治疗方法。癌细胞以三种方式死亡： 凋亡、坏死和自噬。细胞内活性氧显著增加 活性氧（ROS）可以引起不可逆的氧化损伤，导致细胞死亡， 凋亡和坏死。最近，我们的团队创造了一种新颖的SPIO-GOx纳米平台， 协同ROS和代谢消耗疗法。通过体外和体内研究，我们发现 这种纳米平台可以产生非常高水平的ROS和高效的肿瘤细胞， 杀伤性通过靶向递送使该药剂的治疗特性最大化， 最小的全身毒性对于有效的临床转化是至关重要的。经动脉 化疗栓塞（TACE），其中化疗直接输送到肿瘤供血区 动脉，是目前治疗不可切除HCC的标准。TACE协同输送 肿瘤血管栓塞化疗，同时显著降低毒性 由于有针对性的交付。在这个项目中，我们计划利用我们的创新SPIO-GOx 具有经动脉递送技术的治疗诊断纳米平台，以研究 在肝癌治疗中的应用如果成功的话，我们可能会推进肝癌的科学 使用这种新的治疗诊断纳米疗法进行治疗。