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PSMA-TAT双靶点多模态成像探针的构建及其在前列腺癌诊断中的应用

批准号81703466 学科分类药物分析 ( H3010 )
项目负责人刘瑞林 负责人职称讲师 依托单位西安交通大学
资助金额21.00
万元
项目类别青年科学基金项目 研究期限2018 年 01 月 01 日 至
2020 年 12 月 31 日
中文主题词PSMA-TAT双靶点;多模态成像;上转换发光成像;前列腺癌;诊断探针
英文主题词PSMA-TAT dual-targets;Multimodal imaging;Up-conversion luminescence imaging;Prostate cancer;Diagnostic probe

摘要

中文摘要 前列腺癌是男性泌尿生殖系统常见恶性肿瘤之一。实现前列腺癌的高灵敏、精准诊断是当今该领域研究的瓶颈。本项目拟针对缺乏灵敏度高、穿透力深、靶向性强的多模态造影剂而导致前列腺癌诊断困难的问题和难点,制备生物相容性的PSMA-TAT双靶点多模态成像探针。以超小尺寸的稀土上转换纳米粒子为核,采用铁基鞣酸墨水涂层与改性Stober法合成稀土纳米粒子@磁性介孔碳@中空介孔有机硅纳米探针;根据前列腺癌特异性分子靶点的特点,将前列腺特异性膜抗原PSMA与肿瘤细胞核靶向肽TAT键合至诊断探针表面;采用多种表征手段研究诊断探针的理化性质与表面形态;通过体内/外实验考察诊断探针的靶向性与生物安全性;以前列腺癌大鼠为模型,建立高灵敏度、强靶向性的磁共振/超声/光声/上转换发光多模态成像精准诊断前列腺癌的新方法。拟通过本项目的实施,为活体水平下多模态成像诊断前列腺癌提供新方法,也为其它恶性肿瘤的精准诊断提供新思路。
英文摘要 Prostate cancer (PC) is a common malignant tumor in male genitourinary system. Currently, it is still an enormous bottleneck for realizing the high sensitivity and accurate diagnosis of PC. Developing a multimodal contrast agent with higher sensitivity, deeper penetration depth and stronger targetability to solve the diagnosis difficulty of PC will be most desirable from both fundamental and practical points of view. In light of the above-mentioned problems, a PSMA/TAT-dual-targeted imaging probe will be fabricated. Herein, an ultra-small size rare-earth doped upconversion nanoparticles as the core will be firstly prepared, then the multilayered upconversion nanoparticles@magnetic mesoporous carbon@hollow mesoporous organosilica nanoparticles will be obtained by a versatile iron-tannin-framework “ink” coating and modified Stober methods. Based on the characteristics of the specific molecular targets for PC, the prostate specific membrane antigen PSMA and TAT peptides will be covalently bonded onto the surface of the as-obtained diagnostic probe accordingly. The physicochemical properties and surface morphology of the diagnostic probe will be systematically investigated. Targeting property and biological safety of the diagnostic probe will be evaluated in vitro and in vivo. A novel method on the magnetic resonance imaging/photoacoustic tomography/up-conversion luminescence/ultrasound imaging guided diagnosis of PC will be established by using a nude mice model of PC. This project not only provides a new method for the multimodal imaging guided accurate diagnosis of PC in vivo, but also offers a new window for the further study of other malignant tumors.
结题摘要

成果

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