In-Labeled annexin A5-polyethylene glycol–coated core-cross-linked polymeric micelle-Cy7

Apoptosis (programmed cell death) plays an important role in the pathophysiology of many diseases, such as cancers, neurodegenerative disorders, vascular disorders, atherosclerosis, and chronic hepatitis, as well as in the biology of normal cells like epithelial cells and immune cells (1). During apoptosis, there is rapid redistribution of phosphatidylserine (PS) from the inner membrane leaflet to the outer membrane leaflet, exposing the anionic head group of PS. PS is also accessible for annexin V (or annexin A5) binding in necrosis because of disruption of the plasma membrane. Annexin V, a 36-kDa protein, binds to PS with high affinity ( = 7 nM). Annexin V derivatives have been developed for imaging apoptosis as well as necrosis with different imaging modalities such as single-photon emission computed tomography (SPECT) (2-4), positron emission tomography (5), near-infrared (NIR) fluorescence (6), and magnetic resonance imaging (7). Cy5.5-Annexin V has been evaluated as an optical probe in small animals. Annexin V-CLIO-Cy5.5 (AnxCLIO-Cy5.5) is a multimodal agent that consists of CLIO nanoparticles labeled with annexin V and Cy5.5 (6). van Tilborg et al. (7) incorporated annexin A5 into di-stearoyl-polyethylene glycol-phosphatidylethanolamine 2000 (DSPE-PEG2000) micelles labeled with gadolinium-labeled diethylenetriamine pentaacetic acid (Gd-DTPA) and Cy5.5 (annexin A5-Gd-micelles-Cy5.5) for multimodality imaging of atherosclerotic plaques. Zhang et al. (8) conjugated A5 to PEG-coated core-cross-linked polymeric micelles (CCPMs) labeled with Cy7 and In (In-A5-CCPM) for multimodality detection of apoptosis in tumor-bearing mice.