...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Biodegradable Dendritic Positron-emitting Nanoprobes For The Noninvasive Imaging Of Angiogenesis
【24h】

Biodegradable Dendritic Positron-emitting Nanoprobes For The Noninvasive Imaging Of Angiogenesis

机译：可生物降解的树状正电子发射纳米探针用于血管生成的非侵入性成像。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

A biodegradable positron-emitting dendritic nanoprobe targeted at α_vβ_3 integrin, a biological marker known to modulate angiogenesis, was developed for the noninvasive imaging of angiogenesis. The nanoprobe has a modular multivalent core-shell architecture consisting of a biodegradable heterobifunctional dendritic core chemoselectively functionalized with heterobifunctional polyethylene oxide (PEO) chains that form a protective shell, which imparts biological stealth and dictates the pharmacokinetics. Each of the 8 branches of the dendritic core was functionalized for labeling with radiohalogens. Placement of radioactive moieties at the core was designed to prevent in vivo dehalogenation, a potential problem for radiohalogens in imaging and therapy. Targeting peptides of cyclic arginine-glycine-aspartic acid (RGD) motifs were installed at the terminal ends of the PEO chains to enhance their accessibility to α_vβ_3 integrin receptors. This nanoscale design enabled a 50-fold enhancement of the binding affinity to α_vβ_3 integrin receptors with respect to the monovalent RGD peptide alone, from 10,40 nM to 0.18 nM IC_(50). Cell-based assays of the ~(125)l-labeled dendritic nanoprobes using α_vβ_3-positive cells showed a 6-fold increase in α_vβ_3 receptor-mediated endocy-tosis of the targeted nanoprobe compared with the nontargeted nanoprobe, whereas α_vβ_3-negative cells showed no enhancement of cell uptake over time. In vivo biodistribution studies of ~(76)Br-labeled dendritic nanoprobes showed excellent bioavailability for the targeted and nontargeted nanoprobes. In vivo studies in a murine hindlimb ischemia model for angiogenesis revealed high specific accumulation of ~(76)Br-labeled dendritic nanoprobes targeted at α_vβ_3 integrins in angiogenic muscles, allowing highly selective imaging of this critically important process.
机译：针对α_vβ_3整联蛋白的生物可降解正电子发射树突状纳米探针（已知可调节血管生成的生物标记物）被开发用于血管生成的非侵入性成像。纳米探针具有模块化的多价核-壳结构，该结构由可生物降解的异双功能树突状核组成，该化学核心被形成保护壳的异双功能聚环氧乙烷（PEO）链化学选择性地官能化，从而赋予了生物隐身性并决定了药代动力学。树突状核的8个分支中的每一个都被功能化以用放射性卤素标记。放射性部分在核心位置的放置旨在防止体内脱卤素，这是成像和治疗中放射性卤素的潜在问题。将环状精氨酸-甘氨酸-天冬氨酸（RGD）基序的靶向肽安装在PEO链的末端，以增强其与α_vβ_3整联蛋白受体的可及性。相对于单独的单价RGD肽，这种纳米级设计使与α_vβ_3整联蛋白受体的结合亲和力提高了50倍，从10,40 nM到0.18 nM IC_（50）。使用α_vβ_3阳性细胞对〜（125）l标记的树突状纳米探针进行基于细胞的测定，与非靶向纳米探针相比，靶向纳米探针的α_vβ_3受体介导的内吞作用增加了6倍，而α_vβ_3阴性细胞显示随着时间的推移，细胞摄取没有增加。 〜（76）Br标记的树突状纳米探针的体内生物分布研究表明，靶向和非靶向纳米探针具有出色的生物利用度。在鼠后肢局部缺血模型中进行血管生成的体内研究表明，在血管生成性肌肉中，针对α_vβ_3整联蛋白的〜（76）Br标记的树突状纳米探针具有较高的特异性积累，从而可以对该至关重要的过程进行高度选择性的成像。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号