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基于Self-peptide和Fe5C2构建的高敏感MR分子探针对肿瘤血管的MR靶向成像研究

基于Self-peptide和Fe5C2构建的高敏感MR分子探针对肿瘤血管的MR靶向成像研究
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  • 批准号:81501521
  • 批准年度: 2015年
  • 学科分类:分子影像与分子探针(H1808) |
  • 项目负责人:龚明福
  • 负责人职称:讲师
  • 依托单位:中国人民解放军第三军医大学
  • 资助金额:18万元
  • 项目类别:青年科学基金项目
  • 研究期限:2016年01月01日 至 2018年12月31日
  • 中文关键词: Self-peptide;Fe5C2;分子探针;靶向;成像
  • 英文关键词:Magnetic resonance imaging;Tumor blood vessels ;Self-peptide;Fe5C2;PS-b-PAA

项目摘要

中文摘要

血行转移是恶性肿瘤的主要播散途径,肿瘤微血管密度(Microvessel density, MVD)的评估对其分级和转移倾向评价具有重要意义,MR分子成像使其成为可能。但对比剂较低的弛豫效能和靶向投递效能限制了MR分子成像的研究。Fe5C2的饱和磁化强度为140 emu/g,是Fe3O4的2倍,其T2弛豫效能为464.02 mM-1s-1,远远高于Fe3O4的100 mM-1s-1,是迄今报道弛豫效能最高的纳米粒。由两嵌段共聚物PS-b-PAA修饰的纳米粒在水溶液中能自组装成含多个Fe5C2的胶束,进一步提高其弛豫效能。PAA段壳交联能进一步增强胶束的稳定性。Self-peptide是由21个氨基酸组成的CD47分子等效多肽,能抑制巨噬细胞和网状内皮系统的吞噬、清除,并能与高表达于肿瘤血管的αvβ3高亲和力结合。本研究拟基于Fe5C2、PS-b-PAA和Self-peptide构建MR靶向的高敏感、长循环分子探针,以期实现肿瘤血管MR靶向成像。

英文摘要

Blood vessels is the main way for the spread of malignancy, and the accurate assessment of tumor Microvessel density (MVD) in vivo is of great significance for the classification and the transfer tendency evaluation of malignancy, which have been possible based on MR molecular imaging. However, the low relaxivity of the MR contrast agent and the low targeting delivery efficiency of the probe limit the research of MR molecular imaging noticeably. The saturation magnetization intensity of Fe5C2 is 140 emu/g, which is 2 times higher than that of Fe3O4. The particles display an r2 relaxivity of 464.02 mM - 1s- 1, which is far higher than that of Fe3O4 (100 mM - 1s- 1) and is among the highest of all MR probes reported. Nanoparticles coated with amphiphilic block copolymer PS-b-PAA can self-assemble into magnetic micelles containing multiple Fe5C2 in aqueous solution, which further improve the relaxivity of Fe5C2. Shell cross-link of PAA can further improve the stability of the nano micelles. Self-peptide is a kind of CD47 equivalent peptides composed of 21 amino acids, which can inhibit the phagocytosis of the macrophages and RES and combine with integrin high expressed in tumor blood vessels with high affinity. Based on that discussed above, this project want to synthesize a targeted MR molecular probe with high sensitivity based on Fe5C2, PS-b-PAA and Self-peptide, to achieve targeted MR imaging of tumor blood vessels in vivo.

评估说明

    国家自然科学基金项目“基于Self-peptide和Fe5C2构建的高敏感MR分子探针对肿瘤血管的MR靶向成像研究”发布于爱科学iikx,并永久归类于相关科学基金导航中,仅供广大科研工作者查询、学习、选题参考。国科金是根据国家发展科学技术的方针、政策和规划,以及科学技术发展方向,面向全国资助基础研究和应用研究,发挥着促进我国基础研究源头创新的作用。国科金的真正价值在于它能否为科学进步和社会发展带来积极的影响。

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