Protective effect of the apoptosis-sensing nanoparticle AnxCLIO-Cy5.5

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 EditorThis 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.

Graphical AbstractImpact of the apoptosis-sensing nanoparticle, AnxCLIO-Cy5.5, on cell viability: Cell membrane rupture was attenuated in early apoptotic cells exposed to the nanoparticle. Likewise, myocardial infarct size was reduced in mice injected with AnxCLIO-Cy5.5. These effects are likely due to mechanical stabilization of the cell membrane by AnxCLIO-Cy5.5, preventing outward bulging and rupture.Figure optionsDownload high-quality image (212 K)Download as PowerPoint slide