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

• 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
• 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

 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）：原发性和转移性肝脏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% 的肝脏肿瘤患者适合手术治疗，并且单独的全身化疗已被证明疗效有限。微创图像引导介入技术，包括经动脉介入治疗和经皮介入治疗（例如射频消融、激光消融）已被广泛应用于治疗肝细胞癌和肝转移。被引入诊所 然而，这些技术由于不能完全消除癌细胞而受到限制，这可能导致局部肿瘤复发，因此，我们认为迫切需要开发创新的局部治疗方法。动脉内递送的纳米颗粒为高度集中的局部递送热和化疗药物提供了独特的机会，因此可以显着提高肝脏肿瘤的治疗效果。我们开发了一种创新的专有技术，能够介导同步近红外激光触发光热。我们的载有 DOX 的聚乙二醇涂层空心金纳米球 (DOX@PEG-HAuNS) 在正常体温下表现出较低的全身毒性，与激光结合使用时可显着增强抗肿瘤功效。在这个 SBIR 项目中，我们组建了一个多学科团队来实施一致的策略来应对发育和转化挑战。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 DOX@PEG-HAuNS，2) 确定大鼠 IA 注射后 DOX@PEG-HAuNS 的药代动力学 (PK) 和生物分布，以及证明在原位大鼠肝癌模型和临床相关的大型动物肝癌模型（兔 VX2 模型）中同时进行 PTA 和 DOX 化疗的可行性，我们相信所提出的双模式治疗策略将提供。优越的局部肿瘤控制，同时减少不良反应的可能性 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

Doxorubicin-loaded hollow gold nanospheres for dual photothermal ablation and chemoembolization therapy.

负载阿霉素的空心金纳米球用于双重光热消融和化疗栓塞治疗。

• 发表时间: 2020
• 影响因子: 5.7
• 作者: Sheth, Rahul A;Wen, Xiaoxia;Li, Junjie;Melancon, Marites P;Ji, Xin;Wang, Y Andrew;Hsiao, Cheng;Chow, Diana S;Whitley, Elizabeth M;Li, Chun;Gupta, Sanjay
• 通讯作者: Gupta, Sanjay

Interventional Nanotheranostics of Pancreatic Ductal Adenocarcinoma.

胰腺导管腺癌的介入纳米治疗。

• 发表时间: 2016
• 影响因子: 12.4
• 作者: Li, Junjie;Liu, Fengyong;Gupta, Sanjay;Li, Chun
• 通讯作者: Li, Chun

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。

• 发表时间: 2018-05-31
• 影响因子: 4.1
• 作者: Ku, Geng;Huang, Qian;Wen, Xiaoxia;Ye, John;Piwnica;Li, Chun
• 通讯作者: Li, Chun

Cisplatin-loaded hollow gold nanoparticles for laser-triggered release.

用于激光触发释放的负载顺铂的中空金纳米颗粒。

• 发表时间: 2018
• 影响因子: 5.7
• 作者: Xiong, Chiyi;Lu, Wei;Zhou, Min;Wen, Xiaoxia;Li, Chun
• 通讯作者: Li, Chun

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

肝细胞癌：动脉内递送负载阿霉素的空心金纳米球，用于大鼠的光热消融化疗栓塞疗法。

• 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