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

被引:7
作者
Chen, Howard H. [2 ]
Feng, Yan [3 ]
Zhang, Ming [3 ]
Chao, Wei [3 ]
Josephson, Lee [2 ,5 ]
Shaw, Stanley Y. [4 ]
Sosnovik, David E. [1 ,2 ]
机构
[1] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res,CNY, Charlestown, MA 02129 USA
[2] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA
[3] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Charlestown, MA 02129 USA
[4] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA USA
[5] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Translat Nucl Med & Mol Imaging, Charlestown, MA 02129 USA
关键词
Apoptosis; Magnetic nanoparticle; Cardioprotection; Iron oxide; Gene expression; ACUTE MYOCARDIAL-INFARCTION; IRON-OXIDE NANOPARTICLES; ANNEXIN A5; CELL-DEATH; NONINVASIVE DETECTION; REPERFUSION INJURY; IN-VIVO; HEART; PHOSPHATIDYLSERINE; PARTICLES;
D O I
10.1016/j.nano.2011.06.012
中图分类号
TB3 [工程材料学];
学科分类号
082905 [生物质能源与材料];
摘要
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.
引用
收藏
页码:291 / 298
页数:8
相关论文
共 27 条
[1]
Characterization of biophysical and metabolic properties of cells labeled with superparamagnetic iron oxide nanoparticles and transfection agent for cellular MR imaging [J].
Arbab, AS ;
Bashaw, LA ;
Miller, BR ;
Jordan, EK ;
Lewis, BK ;
Kalish, H ;
Frank, JA .
RADIOLOGY, 2003, 229 (03) :838-846
[2]
Will imaging of apoptosis play a role in clinical care? A tale of mice and men [J].
Blankenberg, FG ;
Strauss, HW .
APOPTOSIS, 2001, 6 (1-2) :117-123
[3]
Imaging of apoptosis in the heart with nanoparticle technology [J].
Chen, Howard H. ;
Josephson, Lee ;
Sosnovik, David E. .
WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY, 2011, 3 (01) :86-99
[4]
Real-time imaging of apoptotic cell-membrane changes at the single-cell level in the beating murine heart [J].
Dumont, EA ;
Reutelingsperger, CPM ;
Smits, JFM ;
Daemen, MJAP ;
Doevendans, PAF ;
Wellens, HJJ ;
Hofstra, L .
NATURE MEDICINE, 2001, 7 (12) :1352-1355
[5]
Gidon-Jeangirard C, 1999, J IMMUNOL, V162, P5712
[6]
REPERFUSION INJURY INDUCES APOPTOSIS IN RABBIT CARDIOMYOCYTES [J].
GOTTLIEB, RA ;
BURLESON, KO ;
KLONER, RA ;
BABIOR, BM ;
ENGLER, RL .
JOURNAL OF CLINICAL INVESTIGATION, 1994, 94 (04) :1621-1628
[7]
Visualisation of cell death in vivo in patients with acute myocardial infarction [J].
Hofstra, L ;
Liem, IH ;
Dumont, EA ;
Boersma, HH ;
van Heerde, WL ;
Doevendans, PA ;
DeMuinck, E ;
Wellens, HJJ ;
Kemerink, GJ ;
Reutelingsperger, CPM ;
Heidendal, GA .
LANCET, 2000, 356 (9225) :209-212
[8]
Gene Expression Profiling Reveals Early Cellular Responses to Intracellular Magnetic Labeling with Superparamagnetic Iron Oxide Nanoparticles [J].
Kedziorek, Dorota A. ;
Muja, Naser ;
Walczak, Piotr ;
Ruiz-Cabello, Jesus ;
Gilad, Assaf A. ;
Jie, Chunfa C. ;
Bulte, Jeff W. M. .
MAGNETIC RESONANCE IN MEDICINE, 2010, 63 (04) :1031-1043
[9]
Cell surface-expressed phosphatidylserine and annexin A5 open a novel portal of cell entry [J].
Kenis, H ;
van Genderen, H ;
Bennaghmouch, A ;
Rinia, HA ;
Frederik, P ;
Narula, J ;
Hofstra, L ;
Reutelingsperger, CPM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (50) :52623-52629
[10]
Noninvasive detection of programmed cell loss with 99mTc-labeled annexin A5 in heart failure [J].
Kietselaer, Bas L. J. H. ;
Reutelingsperger, Chris P. M. ;
Boersma, Hendrikus H. ;
Heidendal, Guido A. K. ;
Liem, Ing Han ;
Crijns, Harry J. G. M. ;
Narula, Jagat ;
Hofstra, Leo .
JOURNAL OF NUCLEAR MEDICINE, 2007, 48 (04) :562-567