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（由适用提供）：对原发性和转移性肝肿瘤患者的治疗是挑战未解决的问题。肝脏中肿瘤患者中只有5-20％是手术候选者，仅系统性化疗就证明在治疗肝细胞癌和肝转移方面的效率有限。最低侵入性的图像引导的介入技术，包括散热疗法和经皮干预措施（例如，辐射消融，激光消融），已被引入诊所用于治疗肝肿瘤患者。但是，这些技术受到不完全消除癌细胞的限制，这可能导致局部肿瘤复发。因此，迫切需要为肝肿瘤开发创新的局部治疗方法。我们认为，内部交付的纳米颗粒为高度集中的热量和化学治疗剂提供了独特的机会，因此可能会显着提高肝脏的治疗效率，我们开发了一种具有互联的专有技术，能够介导Simplestaneoles近frared激光触发的光触发光触电（PTA）和DOXORICINAIN（DOXORICINIC）和局部释放。我们的DOX负载的聚乙烯甘油涂层的空心金纳米球（DOX@PEG-HAUNS）在正常体温下显示出低的全身毒性，并且在与激光暴露在高温和平均温度下的激光暴露时会显着提高抗肿瘤效率。在这个SBIR计划中，我们组建了一个多学科团队，以实施一项连贯的战略来应对发展和转化挑战。 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以及与临床相关的大型动物肝癌模型（兔VX2模型）。我们认为，拟议的双模式治疗策略将在减少广告的可能性的同时提供卓越的当地肿瘤控制事件。拟议工作的成功将为DOX@PEG-HAUNS的未来临床试验铺平道路。

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。