Dendritic nanomedicine for cancer imaging and treatment

用于癌症成像和治疗的树突状纳米医学

基本信息

批准号：
8078966
负责人：
CHING-HSUAN TUNG
金额：
$ 30.19万
依托单位：
METHODIST HOSPITAL RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-08-07 至 2013-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8078966
关键词：
Abdominal Cavity Aleurites Aminolevulinic Acid Animal Model Animals Biochemical Biological Assay Cancer Model Cancer Patient Cathepsins Cathepsins B Cell Culture Techniques Cell surface Cells Charge Clinic Clinical Coupled Cysteine Protease Diagnosis Disease Disease Management Dissection Dose Early Diagnosis Early treatment Engineering Enzyme-Linked Immunosorbent Assay Enzymes Epithelial Evaluation Excision Eye Fluorescence Frequencies Goals Hemoglobin High Pressure Liquid Chromatography Image In Situ In Vitro Incubated Injection of therapeutic agent Ligands Light Lighting Location Malignant Neoplasms Malignant neoplasm of ovary Mass Spectrum Analysis Measures Micrometastasis Microscopic Mus Neoplasm Metastasis Oncologist Operative Surgical Procedures Optics Outcome Ovarian Particle Size Pathway interactions Pattern Peptide Hydrolases Peritoneal Photosensitizing Agents Principal Investigator Property Protease Inhibitor Radio Recurrence Recurrent disease Reporter Reporting Research Resected Screening for Ovarian Cancer Sensitivity and Specificity Signal Transduction Solid Neoplasm Source Specificity Staging Structure Surface Technology Testing Therapeutic Effect Tissues Tumor Debulking Tumor Tissue Western Blotting Woman abstracting base cancer cell cancer imaging cancer therapy chemical property cytotoxic cytotoxicity design efficacy testing fluorescence microscope folate-binding protein imaging modality imaging probe improved in vivo irradiation nanomedicine nanoparticle nanoprobe neoplastic cell novel optical imaging programs protein aminoacid sequence protoporphyrin IX research study systems research tumor uptake

项目摘要

DESCRIPTION (provided by applicant): Abstract The goal of this research is to develop a novel targeted protease sensing nanomedicine for early detection and treatment of ovarian cancer. Currently micrometastases within the abdominal cavity is detected by naked eyes; therefore high missing rate has caused recurrence in about 80 90% of women with ovarian cancer. A reliable imaging probe to report micrometastases would be extremely useful in disease management. It has been found that the protease activity of cathepsin B and high level of folate receptor were associated with ovarian cancer. Taking advantages of these unique expression patterns of folate receptor and cathepsin B, we propose to develop a novel nanomedicine with ultra- sensitivity for imaging and specific cytotoxicity for treatment. The assembled nanomedicines are neither fluorescent nor cytotoxic in its initial intact state, but become brightly fluorescent and phototoxic after selective internalization and intracellular activation. The newly developed nanomedicines are expected to have several advantages to treat ovarian cancer: a) high specificity because of regional specific uptake mechanism, b) high sensitivity and potency because of the unique activation mechanism, and c) improved surgical outcome because oncologists could resect micrometastases in completion. Together with recent advances in the field of optical imaging systems, this research is expected to ultimately result in a new clinical photomedicine to help ovarian cancer patients. We believe that the developed approach can be used as a platform to design a broad spectrum of activatable nanomedicine to image and treat other epithelial cancers. Narrative The overall goal of this research is to develop a novel targeted enzyme sensitive nanomedicine to image and treat ovarian cancer. The proposed technology is unique and there are currently no alternatives available for ovarian cancer imaging. The proposed nanomedicine could have vast translational potential and could be introduced into the clinic fairly rapidly following efficacy testing in animal models.

描述（由申请人提供）：摘要本研究的目标是开发一种新型靶向蛋白酶传感纳米药物，用于卵巢癌的早期检测和治疗。目前腹腔内的微转移是通过肉眼检测的；因此，高漏诊率导致约80-90%的卵巢癌女性复发。报告微转移的可靠成像探针对于疾病管理将非常有用。研究发现组织蛋白酶B的蛋白酶活性和叶酸受体的高水平与卵巢癌有关。利用叶酸受体和组织蛋白酶 B 的这些独特表达模式，我们建议开发一种具有超灵敏成像和特定细胞毒性治疗的新型纳米药物。组装的纳米药物在其初始完整状态下既不荧光也不具有细胞毒性，但在选择性内化和细胞内激活后变得明亮的荧光和光毒性。新开发的纳米药物有望在治疗卵巢癌方面具有多种优势：a）由于区域特异性摄取机制而具有高特异性；b）由于独特的激活机制而具有高敏感性和效力；c）由于肿瘤学家可以切除微转移而改善手术结果完成中。结合光学成像系统领域的最新进展，这项研究有望最终产生一种新的临床光医学来帮助卵巢癌患者。我们相信，所开发的方法可以用作设计广泛的可激活纳米药物的平台，以成像和治疗其他上皮癌。叙述这项研究的总体目标是开发一种新型靶向酶敏感纳米药物来成像和治疗卵巢癌。所提出的技术是独特的，目前没有可用于卵巢癌成像的替代技术。所提出的纳米药物可能具有巨大的转化潜力，并且在动物模型中进行功效测试后可以相当快地引入临床。