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Multifunctional Hollow Gold Nanospheres for Concurrent Photothermal-Chemotherapy

用于同步光热化疗的多功能空心金纳米球

基本信息

批准号：
9039018
负责人：
CHUN LI
金额：
$ 50万
依托单位：
OCEAN NANOTECH, LLC
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-04-01 至 2018-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9039018
关键词：
Ablation Address Adverse effects Adverse event Animals Award Biodistribution Body Temperature Cancer Etiology Cancer Model Cessation of life Clinic Clinical Clinical Trials Colorectal Cancer Development Doxorubicin Drug Kinetics Ethanol Future Gold Health Heating Hyperthermia Image Injection of therapeutic agent Intervention Label Laboratories Lasers Lead Light Liver Liver neoplasms Magnetic Resonance Malignant Neoplasms Malignant neoplasm of liver Mediating Metastatic Neoplasm to the Liver Modality Modeling Monitor Nanosphere Nanotechnology National Cancer Institute Neoplasm Metastasis Oceans Operative Surgical Procedures Oryctolagus cuniculus Patients Phase Polyethylene Glycols Positron-Emission Tomography Primary carcinoma of the liver cells Production Radiofrequency Interstitial Ablation Rattus Recurrence Reproducibility Small Business Innovation Research Grant Solid Neoplasm Sterilization Techniques Technology Temperature Therapeutic Embolization Time Toxicology Translating Treatment Efficacy Treatment outcome Tumor Tissue University of Texas M D Anderson Cancer Center Unresectable Work X-Ray Computed Tomography assault cancer cell cancer imaging cancer therapy chemotherapeutic agent chemotherapy clinically relevant cytotoxic good laboratory practice image guided improved individual patient individualized medicine innovation irradiation liver transplantation malignant breast neoplasm melanoma microPET/CT minimally invasive mortality multidisciplinary nanoparticle nanotherapeutic novel outcome forecast preclinical study programs success systemic toxicity treatment strategy tumor uptake

项目摘要

DESCRIPTION (provided by applicant): Treatment of patients with primary and metastatic liver tumors is a challenging unsolved problem. Only 5-20% of patients with tumors in the liver are surgical candidates, and systemic chemotherapy alone has been demonstrated to be of limited efficacy in treating hepatocellular carcinoma and liver metastases. Minimally invasive image-guided interventional techniques, including transarterial interventions and percutaneous interventions (e.g., radiofrequency ablation, laser ablation), have been introduced into the clinic for the treatment of patients with liver tumors. However, these techniques are limited by incomplete elimination of cancer cells, which can lead to local tumor recurrence. Therefore, there is an urgent need to develop innovative local treatment approaches for liver tumors. We believe that intraarterially delivered nanoparticles offers a unique opportunity for highly concentrated local delivery of heat and chemotherapeutic agents and thus may significantly improve the efficacy of treatment for liver tumors. We have developed an innovative proprietary technology that is capable of mediating simultaneous near-infrared laser-triggered photothermal ablation (PTA) and local release of doxorubicin (DOX). Our DOX-loaded, polyethylene glycol-coated hollow gold nanospheres (DOX@PEG-HAuNS) have demonstrated low systemic toxicity under normal body temperatures and significantly enhanced antitumor efficacy when combined with laser exposure under hyperthermia and ablative temperatures. In this SBIR program, we have assembled a multidisciplinary team to implement a coherent strategy to address developmental and translational challenges. Our specific aims are: 1) To synthesize and characterize high-quality DOX@PEG-HAuNS in large scale and under Good laboratory Practice (GLP) production conditions, 2) To determine the pharmacokinetics (PK) and biodistribution of DOX@PEG-HAuNS after IA injection in rats, and to demonstrate the feasibility of concurrent PTA and DOX chemotherapy in an orthotopic rat liver cancer model and a clinically relevant large animal liver cancer model (rabbit VX2 model). We believe that the proposed dual-modality treatment strategy will offer superior local tumor control while reducing the likelihood of adverse events. Success of the proposed work will pave the way for future clinical trials of DOX@PEG-HAuNS.

描述（由申请人提供）：原发性和转移性肝肿瘤患者的治疗是一个具有挑战性的未解决问题。只有5-20%的肝脏肿瘤患者是手术候选者，并且已经证明单独的全身化疗在治疗肝细胞癌和肝转移方面的疗效有限。微创影像引导介入技术，包括经动脉介入和经皮介入（例如，射频消融术、激光消融术）已被引入临床用于治疗肝肿瘤患者。然而，这些技术受到癌细胞不完全消除的限制，这可能导致局部肿瘤复发。因此，迫切需要开发创新的肝脏肿瘤局部治疗方法。我们相信，动脉内递送的纳米颗粒提供了一个独特的机会，高度集中的局部递送热和化疗剂，从而可以显着提高治疗肝肿瘤的疗效。我们开发了一种创新的专有技术，能够同时介导近红外激光触发光热消融（PTA）和阿霉素（DOX）的局部释放。我们的DOX负载的聚乙二醇包覆的中空金纳米球（DOX@PEG-HAuNS）在正常体温下表现出较低的全身毒性，并且当与高温和消融温度下的激光暴露相结合时，显着增强了抗肿瘤功效。在这个SBIR计划中，我们组建了一个多学科团队，以实施连贯的战略来应对发展和翻译挑战。我们的具体目标是：1）在良好实验室规范（GLP）生产条件下大规模合成和表征高质量的DOX@PEG-HAuNS，2）测定大鼠IA注射后DOX@PEG-HAuNS的药代动力学（PK）和生物分布，并在原位大鼠肝癌模型和临床相关的大型动物肝癌模型中证明同时PTA和DOX化疗的可行性（兔VX 2模型）。我们相信，所提出的双模式治疗策略将提供上级局部肿瘤控制，同时减少不良反应的可能性。事件拟议工作的成功将为DOX@PEG-HAuNS未来的临床试验铺平道路。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Hepatocellular Carcinoma: Intra-arterial Delivery of Doxorubicin-loaded Hollow Gold Nanospheres for Photothermal Ablation-Chemoembolization Therapy in Rats.

DOI：
10.1148/radiol.2016152510
发表时间：
2016-11
期刊：
Radiology
影响因子：
19.7
作者：
Li J;Zhou M;Liu F;Xiong C;Wang W;Cao Q;Wen X;Robertson JD;Ji X;Wang YA;Gupta S;Li C
通讯作者：
Li C

Spatial and Temporal Confined Photothermolysis of Cancer Cells Mediated by Hollow Gold Nanospheres Targeted to Epidermal Growth Factor Receptors.

针对表皮生长因子受体的空心金纳米球介导的癌细胞的空间和时间限制光热作用。