Center for Molecular Imaging Research, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA.
Nanomedicine. 2012 Apr;8(3):291-8. doi: 10.1016/j.nano.2011.06.012. Epub 2011 Jun 24.
The diagnostic utility of the apoptosis-sensing nanoparticle (NP), AnxCLIO-Cy5.5, is well established. Here we sought to define the pathophysiological impact of the nanoparticle (NP) on apoptotic cells. Confocal microscopy showed that AnxCLIO-Cy5.5 remained bound to apoptotic cell membranes for 3 hours but by 7 hours had become completely internalized. AnxCLIO-Cy5.5 exposure did not impact energetics, metabolism or caspase-3 activity in apoptotic cells. Gene expression in cells exposed to AnxCLIO-Cy5.5 did not reveal upregulation of pro-inflammatory or cell-death pathways. Moreover, exposure to AnxCLIO-Cy5.5 decreased the frequency of membrane rupture of early apoptotic cells. Similarly, in mice exposed to 1 hour of ischemia -reperfusion, the injection of AnxCLIO-Cy5.5 at the onset of reperfusion reduced infarct size/area at risk by 16.2%. Our findings suggest that AnxCLIO-Cy5.5 may protect apoptotic cells by stabilizing their cell membranes and has the potential to become a theranostic agent, capable of both identifying and salvaging early apoptotic cells. From the Clinical Editor: This study demonstrates that AnxCLIO-Cy5.5 nanoparticles may protect apoptotic cells by cell membrane stabilization and have the potential to become a "theranostic agent" capable of identifying and salvaging early apoptotic cells.
凋亡感应纳米颗粒(NP)AnxCLIO-Cy5.5 的诊断效用已得到充分证实。在这里,我们试图确定纳米颗粒(NP)对凋亡细胞的病理生理影响。共聚焦显微镜显示,AnxCLIO-Cy5.5 仍与凋亡细胞膜结合 3 小时,但到 7 小时时已完全内化。AnxCLIO-Cy5.5 暴露不会影响凋亡细胞的能量代谢或 caspase-3 活性。暴露于 AnxCLIO-Cy5.5 的细胞中的基因表达未显示促炎或细胞死亡途径的上调。此外,暴露于 AnxCLIO-Cy5.5 可降低早期凋亡细胞细胞膜破裂的频率。同样,在接受 1 小时缺血再灌注的小鼠中,在再灌注开始时注射 AnxCLIO-Cy5.5 可使梗死面积/危险区域减少 16.2%。我们的研究结果表明,AnxCLIO-Cy5.5 可能通过稳定细胞膜来保护凋亡细胞,并有可能成为一种治疗诊断剂,既能识别又能挽救早期凋亡细胞。来自临床编辑:这项研究表明,AnxCLIO-Cy5.5 纳米颗粒可能通过细胞膜稳定来保护凋亡细胞,并有可能成为一种“治疗诊断剂”,能够识别和挽救早期凋亡细胞。