Dendritic nanomedicine for cancer imaging and treatment

用于癌症成像和治疗的树突状纳米医学

• 批准号: 7670312
• 负责人: CHING-HSUAN TUNG
• 金额: $ 31.13万
• 依托单位: METHODIST HOSPITAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 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/7670312
• 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; 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

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）：摘要这项研究的目的是开发一种新型的靶向蛋白酶传感纳米医学，用于早期检测和治疗卵巢癌。当前，腹腔内的微型转移被肉眼检测到。因此，大约8090％的卵巢癌女性中的高度缺失率很高。可靠的成像探针报告微转移在疾病管理中非常有用。已经发现，组织蛋白酶B和高水平叶酸受体的蛋白酶活性与卵巢癌有关。利用叶酸受体和组织蛋白酶B的这些独特表达模式的优势，我们建议开发一种具有超敏感性的新型纳米医学，以进行成像和特定的细胞毒性进行治疗。组装的纳米医学既不是荧光，也不是其初始完整状态的细胞毒性，而是在选择性内在化和细胞内激活后变得明亮的荧光和光毒性。新开发的纳米药物预计将具有治疗卵巢癌的几个优势：a）由于区域特异性摄取机制，b）高敏感性和效能高，因为独特的激活机制以及c）改善了手术结果，因为肿瘤学家可以在完成中分辨出微含量。随着光学成像系统领域的最新进展，这项研究有望最终导致新的临床光医学来帮助卵巢癌患者。我们认为，开发的方法可以用作设计广泛的可激活纳米医学的平台，以形象和处理其他上皮癌。叙述这项研究的总体目标是开发一种新型的靶向酶敏感纳米医学来形象和治疗卵巢癌。拟议的技术是独一无二的，目前没有可用于卵巢癌成像的替代方法。提出的纳米医学可能具有巨大的转化潜力，并且在动物模型中有效性测试后，可以很快地引入诊所。