用于定量成像的癌症特异性和器官回避 RNA 结构-猫眼课题宝

用于定量成像的癌症特异性和器官回避 RNA 结构

批准号：

9298655

负责人：

Bernard Mark Evers

金额：

$31.64万

依托单位：

OHIO STATE UNIVERSITY

依托单位国家：

美国

项目类别：

财政年份：

2014

资助国家：

美国

项目状态：

已结题

起止时间：

2014-07-01 至 2019-06-30

来源：

https://reporter.nih.gov/project-details/9298655

关键词：

Adopted Animal Cancer Model Animals Architecture Binding Biological Biological Models Cancer Diagnostics Catalytic RNA Cell Surface Receptors Cells Chemicals Colon Carcinoma Contrast Media Dendrimers Detection Development Disseminated Malignant Neoplasm Dose Dyes Evaluation Future Gadolinium Gene Silencing Genes Goals Image Imaging Techniques In Vitro Injection of therapeutic agent Iowa Ligand Binding Ligands Liver Lung Magnetic Resonance Imaging Malignant Neoplasms Methods MicroRNAs Molecular Monitor Motor Multimodal Imaging Mus Nanotechnology Nature Oncogenic Organ Positron-Emission Tomography Process RNA RNA Transport Radioisotopes Real-Time Systems Reporter Research Resistance Side Signal Transduction Small Interfering RNA Solid Neoplasm System Therapeutic Therapeutic Agents Thermodynamics Time Tissues Toxic effect Urea aptamer base cancer cell cancer imaging clinical application design fluorescence imaging fluorophore image guided image guided therapy image-guided drug delivery imaging agent imaging modality in vivo innovation mouse model nano nanoparticle non-invasive imaging prospective public health relevance quantitative imaging radiotracer response scaffold single photon emission computed tomography stem targeted treatment temporal measurement therapeutic siRNA trafficking tumor tumor heterogeneity uptake

中文摘要

翻译

点击翻译按钮获取中文摘要

英文摘要

DESCRIPTION (provided by applicant): Development of image-guided drug delivery systems for real-time monitoring, quantifying and validating the delivery and therapeutic action is very important for both research and clinical applications. Various multifunctional nanoparticles of different materials have been investigated over the last decade as prospective imaging and therapeutic platforms; however, effective strategies to quantitatively evaluate delivery of therapeutic payloads to tumors and metastatic cancer cells in vivo are challenging due to low efficiency in specific cancer targeting and non-specific trapping in vital organs such as, liver an lungs. Our goal is to adopt an innovative RNA nanotechnology approach to construct ultrastable multifunctional RNA Beacons and RNA Dendrimers as image-guided agents for quantitative real-time assessment of tumor and metastatic cancer targeted therapeutic delivery, distribution, uptake and response. We have shown that our RNA nanoparticles are non-toxic, non-immunogenic and capable of penetrating across heterogeneous biological barriers to deliver high doses of therapeutics specifically to solid tumors and metastatic cells in mice with little accumulation in normal organs. This provides an ideal platform for non-invasive imaging of cancer therapeutics in vivo. Our multifunctional RNA nanoparticles will be designed to harbor: (1) imaging modules: NIR fluorophores for in vivo fluorescence imaging; radionuclides for PET/SPECT imaging; and gadolinium contrast agents for MRI; (2) targeting modules: such as RNA aptamers or chemical ligands for binding to cancer specific cell surface receptors resulting in internalization of RNA nanoparticles into cancer cells; and (3) therapeutic modules: siRNAs and anti-miRNA to silence the expression of oncogenic genes. The multifunctional RNA constructs will then be evaluated in our well established colon cancer animal models. We will employ multimodal imaging techniques (NIRF, PET/SPECT and/or MRI) for monitoring the therapeutic delivery process in real-time at various spatial and temporal resolution scales. This approach is based on the consideration that each of the three imaging modalities has advantages, and an integrated approach will lead to synergistic benefits with regards to image-guided therapy.

期刊论文(9)

专著(0)

科研奖励(0)

会议论文