Applications of Core-Shell Ti02 Nanoconjugates

核壳型TiO2纳米复合物的应用

• 批准号: 8489117
• 负责人: GAYLE E. WOLOSCHAK
• 金额: $ 31.1万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8489117
• 关键词: Animal Model; Animals; Biological Models; Biomedical Research; Biopolymers; Biotechnology; Blood; Catheters; Cell Death; Cells; Cervical; Cervix carcinoma; Cultured Cells; DNA; Development; Disease; Drug Formulations; Funding; Genome; Glucose; Goals; Head and Neck Cancer; Head and Neck Neoplasms; Hepatic artery; Human; Intervention; Interventional radiology; Learning; Length; Lighting; Liver neoplasms; Long-Term Effects; Magnetic Resonance Imaging; Maintenance; Malignant Neoplasms; Malignant neoplasm of liver; Mediating; Modality; Modeling; Modification; Monitor; Nanoconjugate; Oncogenes; Oryctolagus cuniculus; Papilloma; Papillomavirus; Papillomavirus Infections; Peptide Nucleic Acids; Peptides; Primary carcinoma of the liver cells; Production; Proteins; Reactive Oxygen Species; Regulon; System; Testing; Therapeutic; Therapeutic Index; Time; Tissue Harvesting; Tissues; Tumor Tissue; Viral Genome; Viral Proteins; Virus; base; cancer therapy; cell killing; cell transformation; disease characteristic; human disease; improved; in vivo; interest; irradiation; nanocomposite; nanoparticle; neoplastic cell; novel; public health relevance; tumor; uptake

DESCRIPTION (provided by applicant): In this application, we propose to treat liver carcinoma in vivo, in a rabbit VX2 model, using TiO2 based composite nanoconjugates. During the previous funding period, this application was dedicated to the development of TiO2-biopolymer nanoconjugates as new vehicles for biotechnology. These studies found that, dependent on the nanoparticle coating, these nanoconjugates caused DNA scission or interacted with cellular proteins. Both of these activities can be used to interfere with cancer maintenance and progression. In addition, we have developed novel nanocomposites and nanoconjugate formulations that provide increase photocatalytic activity and modulate contrast for magnetic resonance imaging, leading to improved therapeutic potential and allowing for monitoring of composite nanoconjugate's delivery and retention. We now propose to combine these approaches and the rabbit liver carcinoma VX2 model, a cancer that develops due to papilloma virus infection, in order to attempt to use nanoconjugates therapeutically. We will pursue papilloma virus genome targets not only because they provide tumor- specific markers in this system but also because of their relevance to a portion of head and neck tumors and cervical carcinoma which are similarly infected; it is also quite possible that other tumor systems will be shown to have papilloma virus involvement as well. In addition, this system will provide a model for providing information on non-papilloma virus induced tumors and liver metastatic disease. The specific aims of this proposal are: AIM 1. Formulating composite nanoconjugates (CNCs) optimal for E6/E7 control of papilloma transformed cells and for ROS mediated cell destruction. AIM 2. Formulating the optimal combination of CNCs, scintillator nanoparticles and irradiation for E6/E7 control of papilloma transformed cells and for ROS mediated cell destruction. AIM 3. Testing the curative capacity of the two most optimal combinations of CNCs and scintillator NPs at different timepoints post irradiation Rabbit liver carcinoma is a particularly interesting animal model because it mimics well human liver carcinoma and interventional radiology approaches to deliver non-surgical interventions. Namely, the rabbit VX2 tumor model resembles human disease in that it has the disease- characteristic vasculature (the hepatic artery delivers blood to the tumor), and there exists the possibility of using a catheter to deliver therapeutics. In addition, virally induced cancers are an attractive model for targeting with nanoconjugates. Any breakthrough in this system could therefore aid in pursuit of anti-cancer therapies in papilloma induced cancers such as cervical and head and neck cancer.

描述（由申请人提供）：在本申请中，我们提出使用TiO2基复合纳米偶联物在兔VX2模型中治疗肝癌。在之前的资助期间，该申请致力于开发二氧化钛-生物聚合物纳米缀合物，作为生物技术的新载体。这些研究发现，依赖于纳米颗粒涂层，这些纳米偶联物引起DNA断裂或与细胞蛋白质相互作用。这两种活动都可以用来干扰癌症的维持和发展。此外，我们还开发了新型纳米复合材料和纳米共轭物配方，这些配方增加了光催化活性，调节了磁共振成像的对比度，从而提高了治疗潜力，并允许监测复合纳米共轭物的传递和保留。我们现在建议将这些方法与兔肝癌VX2模型（一种由于乳头状瘤病毒感染而发展的癌症）结合起来，以尝试使用纳米偶联物进行治疗。我们将继续研究乳头状瘤病毒基因组靶点，不仅因为它们在这个系统中提供肿瘤特异性标记，还因为它们与头颈部肿瘤和宫颈癌的一部分相似感染的相关性；这也很有可能，其他肿瘤系统将显示有乳头状瘤病毒参与以及。此外，该系统将为提供非乳头状瘤病毒诱导的肿瘤和肝转移疾病的信息提供模型。本提案的具体目标是：目标1。制备复合纳米偶联物（CNCs），用于控制E6/E7乳头瘤转化细胞和ROS介导的细胞破坏。目标2。研究了CNCs、闪烁纳米粒子和辐照的最佳组合，用于控制E6/E7乳头瘤转化细胞和ROS介导的细胞破坏。目标3。在辐照后不同时间点测试两种最优的CNCs和闪烁体NPs组合的治疗能力兔肝癌是一个特别有趣的动物模型，因为它很好地模仿了人类肝癌和介入放射学方法，以提供非手术干预。也就是说，兔VX2肿瘤模型类似于人类疾病，因为它具有疾病特征的血管系统（肝动脉向肿瘤输送血液），并且存在使用导管输送治疗药物的可能性。此外，病毒诱导的癌症是纳米缀合物靶向的一个有吸引力的模型。因此，该系统的任何突破都可能有助于对乳头状瘤诱发的癌症（如宫颈癌和头颈癌）的抗癌治疗。

项目成果

Plutonium uptake and distribution in mammalian cells: molecular vs. polymeric plutonium.

• DOI: 10.3109/09553002.2011.584941
• 发表时间: 2011-10
• 期刊: International journal of radiation biology
• 影响因子: 2.6
• 作者: Aryal BP;Gorman-Lewis D;Paunesku T;Wilson RE;Lai B;Vogt S;Woloschak GE;Jensen MP
• 通讯作者: Jensen MP

Peptide-mediated cancer targeting of nanoconjugates.

• DOI: 10.1002/wnan.121
• 发表时间: 2011-05
• 期刊: WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY
• 影响因子: 8.6
• 作者: Raha, Sumita;Paunesku, Tatjana;Woloschak, Gayle
• 通讯作者: Woloschak, Gayle

Submicron hard X-ray fluorescence imaging of synthetic elements.

合成元素的亚微米硬 X 射线荧光成像。

• DOI: 10.1016/j.aca.2012.01.064
• 发表时间: 2012
• 期刊: Analytica chimica acta
• 影响因子: 6.2
• 作者: Jensen,MarkP;Aryal,BaikunthaP;Gorman-Lewis,Drew;Paunesku,Tatjana;Lai,Barry;Vogt,Stefan;Woloschak,GayleE
• 通讯作者: Woloschak,GayleE

Effects of fluorescent dye coating of metal oxide nanoparticles on DNA scission.

• 发表时间: 2009
• 期刊: The journal of the Robert H. Lurie Cancer Center of Northwestern University
• 作者: C. Doty;E. Brown;A. Wu;T. Paunesku;G. Woloschak

Development of Multi-Scale X-ray Fluorescence Tomography for Examination of Nanocomposite-Treated Biological Samples.

• DOI: 10.3390/cancers13174497
• 发表时间: 2021-09-06
• 期刊: Cancers
• 影响因子: 5.2
• 作者: Chen S;Lastra RO;Paunesku T;Antipova O;Li L;Deng J;Luo Y;Wanzer MB;Popovic J;Li Y;Glasco AD;Jacobsen C;Vogt S;Woloschak GE
• 通讯作者: Woloschak GE