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：
8267728
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 2014-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8267728
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

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 8090% 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.

抽象的这项研究的目的是开发一种新型的靶向蛋白酶感应纳米医学早期发现和治疗卵巢癌。当前的微晶腹腔被肉眼检测到。因此高度缺失造成了大约8090％的卵巢癌女性复发。可靠的成像探针报告微型转移在疾病管理中非常有用。它一直发现组织蛋白酶B和高水平叶酸受体的蛋白酶活性是与卵巢癌有关。利用这些独特的表达模式的优势叶酸受体和组织蛋白酶B，我们建议开发一种新型的纳米医学对成像和特异性细胞毒性的敏感性。组装纳米医学在其初始完整状态下既不是荧光也不是细胞毒性，而是变成选择性内在化和细胞内的明亮荧光和光毒性激活。新开发的纳米医学有望具有几个优势治疗卵巢癌：a）由于区域特异性吸收而高特异性机制，b）由于独特的激活机制，高灵敏度和效力 c）改善手术结果，因为肿瘤学家可以在完成。加上光学成像系统领域的最新进展，这预计研究最终会导致新的临床摄影医学来帮助卵巢癌症患者。我们认为，开发的方法可以用作平台设计一系列可活化的纳米医学来形象和处理其他上皮癌症。叙述这项研究的总体目标是开发一种新颖的靶向酶敏感纳米医学以形象和治疗卵巢癌。提出的技术是独一无二的目前，尚无可用于卵巢癌成像的替代方法。这提出的纳米医学可能具有巨大的转化潜力，可以引入在动物模型中有效性测试后，迅速进入诊所。