BIOADHESIVE POLYMER CONJUGATES WITH ANTICANCER ACTIVITY

具有抗癌活性的生物粘附聚合物结合物

• 批准号: 2695508
• 负责人: JINDRICH H. KOPECEK
• 金额: $ 2.5万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-01 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2695508
• 关键词: DNA topoisomerases; adenocarcinoma; agglutinins; antineoplastics; biomaterial development /preparation; camptothecin; cell membrane; chemical binding; chemical conjugate; chemical structure; chemical synthesis; colon neoplasms; copolymer; drug design /synthesis /production; drug screening /evaluation; enzyme inhibitors; human tissue; laboratory rat; neoplasm /cancer chemotherapy; neoplastic cell; pharmacokinetics

The parent project is devoted to the development of bioadhesive, biorecognizable anti-inflammatory polymer conjugates for the treatment of colon disease. This proposed FIRCA application extends these studies into the development of bioadhesive, biorecognizable anticancer polymer conjugates for the treatment of colorectal adenocarcinoma. These systems will be based on the concept of binding of N-(2-Hydroxypropyl) methacrylamide (HPMA) copolymer-peanut agglutinin (PNA)-9- aminocamptothecin (9-AC) conjugates to diseased sites by specific PNA- glycoprotein interactions, and on the concept of site-specific release of 9-AC by microbial enzymes present only in the colon. The aim is to design efficient conjugates targetable directly to the cancer tissue. The application also proposes to study the relationship between the structure of the copolymer conjugates and 9-AC release in vitro and in vivo. Both rat and human tissues will be used, and the correlation between animal and human data will be established.

母项目致力于开发生物粘合剂， 用于治疗的生物可识别的抗炎聚合物缀合物 结肠疾病。 这项拟议的FIRCA应用程序扩展了这些研究 开发生物粘附性，生物可识别的抗癌聚合物， 用于治疗结肠直肠腺癌的缀合物。 这些 系统将基于N-（2-羟丙基） 甲基丙烯酰胺（HPMA）-花生凝集素（PNA）-9- 氨基喜树碱（9-AC）通过特异性PNA结合至患病部位- 糖蛋白的相互作用，并对网站的概念，具体的释放 9-AC的微生物酶只存在于结肠。 目的是 设计可直接靶向癌组织的有效缀合物。 该申请还建议研究 共聚物缀合物的结构和9-AC在体外和体内的释放 vivo. 将使用大鼠和人体组织，并且相关性 将建立动物和人类数据之间的关系。