title: Annexin A5-functionalized bimodal lipid-based contrast agents for the detection of apoptosis.
abstract: Apoptosis, or programmed cell death, plays an important role in the etiology of a variety of diseases, including cancer and myocardial infarction. Visualization of apoptosis would allow both early detection of therapy efficiency and evaluation of disease progression. To that aim, we synthesized two types of lipid-based bimodal contrast agents that enable the detection of apoptotic cells with both MRI and optical techniques. MR contrast was provided either by entrapment of iron oxide particles within pegylated micelles or by incorporation of Gd-DTPA-bis(stearylamide) (Gd-DTPA-BSA) lipids within the lipid bilayer of pegylated liposomes. The resulting contrast agents were approximately 10 and 100 nm in diameter, respectively. Additional fluorescent lipids were incorporated in the lipid (bi)layer of the contrast agents to allow parallel detection with optical methods. Multiple human recombinant annexin A5 molecules were covalently coupled to introduce specificity for apoptotic cells. Both annexin A5-conjugated contrast agents were shown to significantly increase the relaxation rates of apoptotic cell pellets compared to untreated control cells and apoptotic cells that were treated with nonfunctionalized nanoparticles. Increased relaxation rates were confirmed to originate from association of the contrast agents to apoptotic cells by confocal microscopy. The targeted nanoparticles presented in this study, which differ both in size and in magnetic properties, may have applications for the in vivo detection of apoptosis.
authors.affiliation: Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands.
authors.forename: Geralda A F
authors.initials: GA
authors.lastname: van Tilborg
authors.forename: Willem J M
authors.initials: WJ
authors.lastname: Mulder
authors.forename: Niko
authors.initials: N
authors.lastname: Deckers
authors.forename: Gert
authors.initials: G
authors.lastname: Storm
authors.forename: Chris P M
authors.initials: CP
authors.lastname: Reutelingsperger
authors.forename: Gustav J
authors.initials: GJ
authors.lastname: Strijkers
authors.forename: Klaas
authors.initials: K
authors.lastname: Nicolay
mesh_terms: D017304:Annexin A5 / Q000737:chemistry* / Q000378:metabolism*; D017209:Apoptosis; D020285:Cryoelectron Microscopy; D006801:Humans; D019169:Jurkat Cells; D008055:Lipids / Q000737:chemistry*; D046529:Microscopy, Electron, Transmission; D049329:Nanostructures / Q000737:chemistry / Q000648:ultrastructure; D010718:Phosphatidylserines / Q000737:chemistry
chemical_list: D017304:Annexin A5; D008055:Lipids; D010718:Phosphatidylserines