Linking Proteins with Anionic Nanoparticles via Protamine: Ultrasmall Protein‐Coupled Probes for Magnetic Resonance Imaging of Apoptosis

Schellenberger, Eyk; Schnorr, Jörg; Reutelingsperger, Chris; Ungethüm, L; Meyer, Wolfdietrich; Taupitz, Matthias; Hamm, Bernd

doi:10.1002/smll.200700847

Cited by 56 publications

(40 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, significant non-specific association was observed after incubation with M1234-VSOP, i.e. the mutant annexin A5-VSOP that does not bind to PS (14). Such non-specific binding was not observed for non-functionalized CLIO (10), superparamagnetic micelles (13) or the basic microbeads used in the present study.…”

Section: Discussioncontrasting

confidence: 78%

“…Bimodal imaging was also enabled by fluorescently labeled micelles with an iron oxide core after covalent coupling of annexin A5 (13). More recently, annexin A5-VSOPs (very small iron oxide particles) were introduced as a novel MR contrast agent for the detection of apoptosis (14). As an alternative to annexin A5, iron oxide particles have also been labeled with the phosphatidylserine-binding C2A domain of the protein synaptotagmin I, which successfully allowed the detection of apoptotic cells both in vitro (15) and in vivo (16).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Internalization of annexin A5‐functionalized iron oxide particles by apoptotic Jurkat cells

Tilborg

Geelen

Duimel

et al. 2009

Contrast Media & Molecular

View full text Add to dashboard Cite

Apoptosis plays an important role in the etiology of various diseases. Several studies have reported on the use of annexin A5-functionalized iron oxide particles for the detection of apoptosis with MRI, both in vitro and in vivo. The protein annexin A5 binds with high affinity to the phospholipid phosphatidylserine, which is exposed in the outer leaflet of the apoptotic cell membrane. When co-exposed to apoptotic stimuli, this protein was shown to internalize into endocytic vesicles. Therefore in the present study we investigated the possible internalization of commercially available annexin A5-functionalized iron oxide particles (r1 = 34.0 +/- 2.1 and r2 = 205.0 +/- 10.4 mm(-1) s(-1) at 20 MHz), and the effects of their spatial distribution on relaxation rates R2*, R2 and R1. Two different incubation procedures were performed, where (1) Jurkat cells were either incubated with the contrast agent after induction of apoptosis or (2) Jurkat cells were simultaneously incubated with the apoptotic stimulus and the contrast agent. Transmission electron microscopy images and relaxation rates showed that the first incubation strategy mainly resulted in binding of the annexin A5-iron oxide particles to the cell membrane, whereas the second procedure allowed extensive membrane-association as well as a small amount of internalization. Owing to the small extent of internalization, only minor differences were observed between the DeltaR2*/DeltaR2 and DeltaR2/DeltaR1 ratios of cell pellets with membrane-associated or internalized annexin A5 particles. Only the increase in R1 (DeltaR1) appeared to be diminished by the internalization. Internalization of annexin A5-iron oxide particles is also expected to occur in vivo, where the apoptotic stimulus and the contrast agent are simultaneously present. Where the extent of internalization in vivo is similar to that observed in the present study, both T2- and T2*-weighted MR sequences are considered suitable for the detection of these particles in vivo.

show abstract

Section: Discussioncontrasting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Internalization of annexin A5‐functionalized iron oxide particles by apoptotic Jurkat cells

Tilborg

Geelen

Duimel

et al. 2009

Contrast Media & Molecular

View full text Add to dashboard Cite

show abstract

“…Successful MR imaging of apoptotic cells in vivo was able to be performed using targeted SPIO against phosphatidylserine after the conjugation of SPIO with the C2 domain of synaptotagmin I [130], annexin V [131], or annexin A5 [132].…”

Section: Apoptosis Imagingmentioning

confidence: 99%

Superparamagnetic Iron Oxide Nanoparticles in Biomedicine: Applications and Developments in Diagnostics and Therapy

Ittrich¹,

Peldschus²,

Raabe³

et al. 2013

Fortschr Röntgenstr

125

101

View full text Add to dashboard Cite

Superparamagnetic iron oxide nanoparticles (SPIO) can be used to image physiological processes and anatomical, cellular and molecular changes in diseases. The clinical applications range from the imaging of tumors and metastases in the liver, spleen and bone marrow, the imaging of lymph nodes and the CNS, MRA and perfusion imaging to atherosclerotic plaque and thrombosis imaging. New experimental approaches in molecular imaging describe undirected SPIO trapping (passive targeting) in inflammation, tumors and associated macrophages as well as the directed accumulation of SPIO ligands (active targeting) in tumor endothelia and tumor cells, areas of apoptosis, infarction, inflammation and degeneration in cardiovascular and neurological diseases, in atherosclerotic plaques or thrombi. The labeling of stem or immune cells allows the visualization of cell therapies or transplant rejections. The coupling of SPIO to ligands, radio- and/or chemotherapeutics, embedding in carrier systems or activatable smart sensor probes and their externally controlled focusing (physical targeting) enable molecular tumor therapies or the imaging of metabolic and enzymatic processes. Monodisperse SPIO with defined physicochemical and pharmacodynamic properties may improve SPIO-based MRI in the future and as targeted probes in diagnostic magnetic resonance (DMR) using chip-based ?NMR may significantly expand the spectrum of in vitro analysis methods for biomarker, pathogens and tumor cells. Magnetic particle imaging (MPI) as a new imaging modality offers new applications for SPIO in cardiovascular, oncological, cellular and molecular diagnostics and therapy. Key Points: Citation Format:

show abstract

“…In addition, several stable and biocompatible magnetic fl uids have been prepared by coating magnetic nanoparticles with proteins, such as human serum albumin ( HSA ) [123] , avidin [124] , and Annexin A5 (anxA5) -VSOP [125] .…”

Section: Modifi Cation Using Polymeric Stabilizersmentioning

confidence: 99%

Magnetic Nanomaterials asMRIContrast Agents

Gun’ko

Brougham

2009

Nanotechnologies for the Life Sciences

View full text Add to dashboard Cite

The sections in this article are Introduction Classification of Magnetic Nanomaterials Used for MRI Applications Magnetic Oxide‐Based Nanoparticles Magnetic Metal‐ and Alloy‐Based Nanoparticles as Contrast Agents Rare Earth Metal‐Loaded Nanoparticulate Contrast Agents Coating and Surface Functionalization of Magnetic Nanoparticles Surface Modification with Monomeric Stabilizers Modification Using Polymeric Stabilizers Modification Using Inorganic Coatings Vectorization of Magnetic Nanomaterials for Targeted Imaging Properties and Characterization of Magnetic Nanoparticle Suspensions Characterizing the Suspensions Nanoparticle Size: Transmission Electron Microscopy Magnetic Properties: Magnetometry Hydrodynamic Size: Photon Correlation Spectroscopy Magnetic Resonance Properties: Nuclear Magnetic Resonance Dispersion NMR Relaxation in the Presence of Superparamagnetic Nanoparticles SPM Theory Applied to Suspensions of Nanoparticle Clusters General Application of Relaxation Time Measurements Application of Magnetic Nanomaterials in MRI Current Clinical Applications Gastrointestinal Tract and Bowel Imaging Liver and Spleen Imaging Lymph Node Imaging Bone Marrow Imaging Brain Imaging Blood Pool Imaging and MR Angiography Atherosclerosis Imaging Potential Clinical Applications Cellular Labeling and Tracking Molecular Imaging Summary and Future Outlook Improved Imaging Methods Improved Imaging Hardware Improved Contrast Agents

show abstract

Linking Proteins with Anionic Nanoparticles via Protamine: Ultrasmall Protein‐Coupled Probes for Magnetic Resonance Imaging of Apoptosis

Cited by 56 publications

References 17 publications

Internalization of annexin A5‐functionalized iron oxide particles by apoptotic Jurkat cells

Internalization of annexin A5‐functionalized iron oxide particles by apoptotic Jurkat cells

Superparamagnetic Iron Oxide Nanoparticles in Biomedicine: Applications and Developments in Diagnostics and Therapy

Magnetic Nanomaterials asMRIContrast Agents

Contact Info

Product

Resources

About