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

Nanomedicine. 2012 Apr;8(3):291-8. doi: 10.1016/j.nano.2011.06.012. Epub 2011 Jun 24.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Annexins / pharmacology*
  • Apoptosis / drug effects*
  • Apoptosis / genetics
  • CHO Cells
  • Carbocyanines / pharmacology*
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Cricetinae
  • Cricetulus
  • Energy Metabolism / drug effects
  • Flow Cytometry
  • Gene Expression Profiling
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Confocal
  • Nanoparticles / chemistry*
  • Protective Agents / pharmacology*
  • Reperfusion Injury / pathology

Substances

  • Annexins
  • Carbocyanines
  • Cy5.5-annexin V conjugate
  • Protective Agents