title: Protective effect of the apoptosis-sensing nanoparticle AnxCLIO-Cy5.5.
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.
authors.affiliation: Center for Molecular Imaging Research, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA.
authors.forename: Howard H
authors.initials: HH
authors.lastname: Chen
authors.forename: Yan
authors.initials: Y
authors.lastname: Feng
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Chao
authors.forename: Lee
authors.initials: L
authors.lastname: Josephson
authors.forename: Stanley Y
authors.initials: SY
authors.lastname: Shaw
authors.forename: David E
authors.initials: DE
authors.lastname: Sosnovik
mesh_terms: D000818:Animals; D017302:Annexins / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D016466:CHO Cells; D002232:Carbocyanines / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D004734:Energy Metabolism / Q000187:drug effects; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry*; D020011:Protective Agents / Q000494:pharmacology*; D015427:Reperfusion Injury / Q000473:pathology
chemical_list: D017302:Annexins; D002232:Carbocyanines; C506056:Cy5.5-annexin V conjugate; D020011:Protective Agents