Tumor casting hydrogels for interventional radiology treatment of hepatocellular carcinoma

肿瘤铸造水凝胶用于肝细胞癌介入放射治疗

基本信息

批准号：
10397989
负责人：
David Peter Cormode
金额：
$ 24.38万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-01 至 2025-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10397989
关键词：
Autophagocytosis Biodistribution Biology Blood Vessels Blood capillaries Blood flow Body Temperature Cancer Etiology Cessation of life Characteristics Chemicals Chemoembolization Chitosan Cirrhosis Clinical Trials Contrast Media Crosslinker Cytotoxic agent Development Dose Doxorubicin Drug Delivery Systems Drug usage Emulsions Encapsulated Ensure Fluoroscopy Formulation Funding Gel Generations Hot Spot Hydrogels Image Imaging Techniques In Vitro Incidence Industrialization Injectable Injections Intervention Interventional radiology Iron Ischemia Kidney Label Lead Magnetic Resonance Imaging Malignant Epithelial Cell Malignant Neoplasms Malignant neoplasm of liver Methods Microspheres Monitor Neoplasms in Vascular Tissue Obstruction Patient-Focused Outcomes Patients Penetration Pharmaceutical Preparations Photons Polysaccharides Positioning Attribute Primary carcinoma of the liver cells Procedures Property Rattus Recurrent disease Research Residual state Rheology Roentgen Rays Scanning Survival Rate System Technology Therapeutic Therapeutic Embolization Time Toxicology United States United States National Institutes of Health Unresectable Viscosity Visualization Work X-Ray Computed Tomography X-Ray Medical Imaging anti-cancer antitumor effect attenuation biomaterial compatibility clinical translation cytotoxicity drug development efficacy study efficacy testing feeding image guided improved improved outcome in vivo inhibitor iron oxide nanoparticle liver cancer model liver cancer patient minimally invasive nanoGold novel public health relevance radiologist safety study standard of care targeted delivery targeted treatment tumor tumor vascular supply

项目摘要

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.

项目摘要肝细胞癌（HCC）是美国与癌症相关死亡的最快崛起原因。之一用于HCC的主要治疗方法是栓塞，即阻塞用肿瘤喂养的血管微粒。毒品洗脱珠（DEB）经常用于此目的。尽管发展了 DEB，患者的存活率仅为5年。这可能是由于药物洗脱的特征不佳和与肿瘤毛细血管的大小相比，由于珠子很大，因此不完全栓塞。同时，通常，这些珠子无法通过成像可视化，因此评估它们的珠子在过程中成功部署。因此，可以开发可生物降解的材料阻塞血管，具有可调药的释放，并将材料与放射性特性结合在一起，将是有利的。我们提出了一种新颖的注射，热敏感，放射性和药物洗脱水凝胶作为HCC治疗的治疗平台，它将完全阻塞肿瘤血管。肾脏可清除的金纳米颗粒（AUNP）将用于呈现凝胶射道 X射线衰减，出色的生物相容性，最终可以排出。在这项拟议的研究中， AUNP/药物负载的水凝胶将被合成，并在物理和化学上表征。体内研究凝胶的对比性产生特性，其抗肿瘤作用，其生物分布和清除将进行。这项工作的结果将为额外的功效和安全性奠定基础在临床翻译之前需要进行研究。

项目成果

期刊论文数量（1）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Ytterbium Nanoparticle Contrast Agents for Conventional and Spectral Photon-Counting CT and Their Applications for Hydrogel Imaging.

DOI：
10.1021/acsami.2c12354
发表时间：
2022-08-31
期刊：
ACS APPLIED MATERIALS & INTERFACES
影响因子：
9.5
作者：
Dong, Yuxi C.;Kumar, Ananyaa;Rosario-Berrios, Derick N.;Si-Mohamed, Salim;Hsu, Jessica C.;Nieves, Lenitza M.;Douek, Philippe;Noel, Peter B.;Cormode, David P.
通讯作者：
Cormode, David P.