Bioresponsive nanosensors in medical imaging

Schellenberger, Eyk

doi:10.1098/rsif.2009.0336.focus

Cited by 17 publications

(8 citation statements)

References 36 publications

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“…1c). This molecular ratio was proportionally higher than previously synthesized ANX conjugates with smaller nanoparticles (e.g., 4–5:1 ANX:iron oxide ratio) (22, 23).…”

Section: Resultscontrasting

confidence: 51%

A molecular MRI probe to detect treatment of cardiac apoptosis in vivo

Dash

Chung

Chan

et al. 2011

Magnetic Resonance in Med

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Cell death by apoptosis is critical in myocardial diseases, and noninvasive detection of early, reversible apoptosis might be useful clinically. Exogenous Annexin-V (ANX) protein binds membrane phosphatidylserine, which is externalized in early apoptosis. A molecular MRI probe was constructed with superparamagnetic iron oxide (SPIO) conjugated to recombinant human ANX (ANX-SPIO). Apoptosis was induced with doxorubicin, a cardiotoxic cancer drug, in culture in neonatal rat ventricular myocytes, cardiac fibroblasts, and mesenchymal stem cells, and in vivo in the mouse heart. ANX-SPIO was validated using T2*-weighted 3T MRI. ANX-SPIO produced T2* signal loss, reflecting iron content, that correlated highly with independent apoptosis markers; bound with high affinity to apoptotic myocytes by competition assay (Ki 69 nM); detected apoptosis in culture much earlier than did TUNEL stain; and revealed fibroblast resistance to apoptosis. With apoptosis in vivo, ANX-SPIO produced diffuse myocardial T2* signal loss that correlated with increased iron stain and caspase activity. Treatment with an alpha-1-adrenergic agonist in vivo reversed apoptosis and eliminated the ANX-SPIO MRI signal. It is concluded that cardiac MRI of ANX-SPIO detects early, nonischemic cardiac apoptosis in culture and in vivo, and can identify reversibly injured cardiac cells in diseased hearts, when treatment is still possible. Magn Reson Med 66:1152-1162,

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“…1c). This molecular ratio was proportionally higher than previously synthesized ANX conjugates with smaller nanoparticles (e.g., 4–5:1 ANX:iron oxide ratio) (22, 23).…”

Section: Resultscontrasting

confidence: 51%

A molecular MRI probe to detect treatment of cardiac apoptosis in vivo

Dash

Chung

Chan

et al. 2011

Magnetic Resonance in Med

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“…Activatable imaging probes amplify output signals in response to a specific biomolecular recognition or an environmental change in real time [77]. The unique characteristics of activatable fluorescence molecular probes could provide higher signal-to-background ratios compared to conventional “constantly active” fluorescent probes.…”

Section: Nirf Nanoprobes For Cancer Molecular Imagingmentioning

confidence: 99%

Near-infrared fluorescent nanoprobes for cancer molecular imaging: status and challenges

Gao

Gambhir

et al. 2010

Trends in Molecular Medicine

199

141

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Near-infrared fluorescence (NIRF) imaging promises to improve cancer imaging and management; advances in nanomaterials allow scientists to combine new nanoparticles with NIRF imaging techniques, thereby fulfilling this promise. Here, we present a synopsis of current developments in NIRF nanoprobes, their use in imaging small living subjects, their pharmacokinetics and toxicity and finally their integration into multimodal imaging strategies. We also discuss challenges impeding the clinical translation of NIRF nanoprobes for molecular imaging of cancer. Whereas utilization of most NIRF nanoprobes remains at a proof-of-principle stage, optimizing the impact of nanomedicine in cancer patient diagnosis and management will likely be realized through persistent interdisciplinary amalgamation of diverse research fields. Keywords NIRF nanoprobes; molecular imaging; clinical translation; QDs; nanotubes Molecular imaging and nanotechnologyCancer molecular imaging is an evolving field in which diverse optical tools and strategies are used for early detection and management of tumors. This field arose from the merger of several pre-existing disciplines such as modern cancer molecular biology, chemistry and imaging technologies. Consequently, cancer molecular imaging has created unique opportunities to study and noninvasively monitor tumor genesis, development and

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“…MMPs play a crucial role in normal physiology by digesting extracellular matrix proteins, for example, in tissue development and homeostasis, as well as in many pathologic conditions, for example, tissue repair, cancer, and chronic inflammatory vascular and joint diseases. [4][5][6][7] Most MMPs are secreted as latent proenzymes and become activated on enzymatic cleavage. Two prominent members of this family, the gelatinases MMP-2 and MMP-9, are highly expressed in several types of human cancers.…”

Section: S Uperparamagnetic Iron Oxide Nanoparti-mentioning

confidence: 99%

Combined in Situ Zymography, Immunofluorescence, and Staining of Iron Oxide Particles in Paraffin-Embedded, Zinc-Fixed Tissue Sections

et al. 2012

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Superparamagnetic iron oxide particles are used as potent contrast agents in magnetic resonance imaging. In histology, these particles are frequently visualized by Prussian blue iron staining of aldehyde-fixed, paraffin-embedded tissues. Recently, zinc saltbased fixative was shown to preserve enzyme activity in paraffin-embedded tissues. In this study, we demonstrate that zinc fixation allows combining in situ zymography with fluorescence immunohistochemistry (IHC) and iron staining for advanced biologic investigation of iron oxide particle accumulation. Very small iron oxide particles, developed for magnetic resonance angiography, were applied intravenously to BALB/c nude mice. After 3 hours, spleens were explanted and subjected to zinc fixation and paraffin embedding. Cut tissue sections were further processed to in situ zymography, IHC, and Prussian blue staining procedures. The combination of in situ zymography as well as IHC with subsequent Prussian blue iron staining on zinc-fixed paraffin-embedded tissues resulted in excellent histologic images of enzyme activity, protease distribution, and iron oxide particle accumulation. The combination of all three stains on a single section allowed direct comparison with only moderate degradation of fluorescein isothiocyanate-labeled substrate. This protocol is useful for investigating the biologic environment of accumulating iron oxide particles, with excellent preservation of morphology.

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Bioresponsive nanosensors in medical imaging

Cited by 17 publications

References 36 publications

A molecular MRI probe to detect treatment of cardiac apoptosis in vivo

A molecular MRI probe to detect treatment of cardiac apoptosis in vivo

Near-infrared fluorescent nanoprobes for cancer molecular imaging: status and challenges

Combined in Situ Zymography, Immunofluorescence, and Staining of Iron Oxide Particles in Paraffin-Embedded, Zinc-Fixed Tissue Sections

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