Human ferritin cages for imaging vascular macrophages

Terashima, Masahiro; Uchida, Masaki; Kosuge, Hisanori; Tsao, Philip S.; Young, Mark; Conolly, Steven M.; Douglas, Trevor; McConnell, Michael V.

doi:10.1016/j.biomaterials.2010.09.029

Cited by 109 publications

(121 citation statements)

References 39 publications

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“…recently. [27][28][29][30][31][32][33][34][35] To prepare the AFt-Au nanoconstruct, Au nanoparticles were biomimetically synthesized inside the cavity of apoferritin by the in situ reduction of sequestered AuCl 4 À ions with NaBH 4 . 36,37 Transmission electron microscopy (TEM) of puried samples aer negative staining showed discrete electron dense dots surrounded by bright (unstained) coronae, conrming that a single Au nanoparticle with a mean size of 3.0 nm was encapsulated within each of the protein nano-cages ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Bio-inspired protein–gold nanoconstruct with core–void–shell structure: beyond a chemo drug carrier

Liu¹,

Wei²,

Huang³

et al. 2013

J. Mater. Chem. B

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Chemotherapy has been widely used in clinical practice for cancer treatment. A major challenge for a successful chemotherapy is to potentiate the anticancer activity, whilst reducing the severe side effects. In this context, we design a bio-inspired protein-gold nanoconstruct (denoted as AFt-Au hereafter) with a core-void-shell structure which exhibits a high selectivity towards carcinoma cells. Anticancer drug 5-fluorouracil (5-FU) can be sequestered into the void space of the construct to produce an integrated nanoscale hybrid AFt-AuFU that exhibits an increased cellular uptake of 5-FU. More importantly, AFt-Au, serving as a bio-nano-chemosensitizer, renders carcinoma cells more susceptible to 5-FU by cell-cycle regulation, and thus, leads to a dramatic decrease of the IC 50 value (i.e. the drug concentration required to kill 50% of the cell population) of 5-FU in HepG2 cells from 138.3 mM to 9.2 mM. Besides HepG2 cells, a remarkably enhanced anticancer efficacy and potentially reduced side effects are also achieved in other cell lines. Our further work reveals that the drug 5-FU is internalized into cells with AFt-Au primarily via receptor-mediated endocytosis (RME). After internalization, AFt-AuFU colocalizes with lysosomes which trigger the release of 5-FU under acidic conditions. Overall, our approach provides a novel procedure in nanoscience that promises an optimal chemotherapeutic outcome.Scheme 1 Design and construction of the AFt-AuFU nanoconstruct. AFt-Au was prepared by reducing AuCl 4À ions with NaBH 4 in the cavity of apoferritin. 5-FU was sequestered into the resulting void space of the AFt-Au complex by passive diffusion through the molecular channels in the apoferritin shell to produce a drug-loaded hybrid nanoconstruct (AFt-AuFU).

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Section: Resultsmentioning

confidence: 99%

Bio-inspired protein–gold nanoconstruct with core–void–shell structure: beyond a chemo drug carrier

Liu¹,

Wei²,

Huang³

et al. 2013

J. Mater. Chem. B

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“…Macrophage-rich carotid lesions were induced in FVB mice as described previously (22,32). Briefly, 8-wk-old mice were fed a highfat diet (HFD) for 4 wk.…”

Section: Animals and Model Inductionmentioning

confidence: 99%

Dual-Modality Activity-Based Probes as Molecular Imaging Agents for Vascular Inflammation

Withana

Saito

et al. 2016

J Nucl Med

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Macrophages are cellular mediators of vascular inflammation and are involved in the formation of atherosclerotic plaques. These immune cells secrete proteases such as matrix metalloproteinases and cathepsins that contribute to disease formation and progression. Here, we demonstrate that activity-based probes (ABPs) targeting cysteine cathepsins can be used in murine models of atherosclerosis to noninvasively image activated macrophage populations using both optical and PET/CT methods. The probes can also be used to topically label human carotid plaques demonstrating similar specific labeling of activated macrophage populations. Methods: Macrophage-rich carotid lesions were induced in FVB mice fed on a high-fat diet by streptozotocin injection followed by ligation of the left common carotid artery. Mice with carotid atherosclerotic plaques were injected with the optical or dual-modality probes BMV109 and BMV101, respectively, via the tail vein and noninvasively imaged by optical and small-animal PET/CT at different time points. After noninvasive imaging, the murine carotid arteries were imaged in situ and ex vivo, followed by immunofluorescence staining to confirm target labeling. Additionally, human carotid plaques were topically labeled with the probe and analyzed by both sodium dodecyl sulfate polyacrylamide gel electrophoresis and immunofluorescence staining to confirm the primary targets of the probe. Results: Quantitative analysis of the signal intensity from both optical and PET/CT imaging showed significantly higher levels of accumulation of BMV109 and BMV101 (P , 0.005 and P , 0.05, respectively) in the ligated left carotid arteries than the right carotid or healthy arteries. Immunofluorescence staining for macrophages in cross-sectional slices of the murine artery demonstrated substantial infiltration of macrophages in the neointima and adventitia of the ligated left carotid arteries compared with the right. Analysis of the human plaque tissues by sodium dodecyl sulfate polyacrylamide gel electrophoresis confirmed that the primary targets of the probe were cathepsins X, B, S, and L. Immunofluorescence labeling of the human tissue with the probe demonstrated colocalization of the probe with CD68, elastin, and cathepsin S, similar to that observed in the experimental carotid inflammation murine model. Conclusion: We demonstrate that ABPs targeting the cysteine cathepsins can be used in murine models of atherosclerosis to noninvasively image activated macrophage populations using both optical and PET/CT methods. The probes could also be used to topically label human carotid plaques demonstrating similar specific labeling of activated macrophage populations. Therefore, ABPs targeting the cysteine cathepsins are potentially valuable new reagents for rapid and noninvasive imaging of atherosclerotic disease progression and plaque vulnerability.

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“…Superparamagnetic iron oxide (SPIO)-labeled cells can be detected as low signal on T2*-weighted sequences with a high sensitivity for inflammation. 16 Iron-based nanoparticle tracers have been preclinically tested in murine models of carotid inflammation, such as engineered human ferritin protein cages encapsulating a magnetite nanoparticle 17 and FeCo/graphiticcarbon nanocrystals. 18 Another technique targeting phagocytes is 19 Fluorine MRI (19F-MRI) utilizing perfluorocarbon- …”

Section: Phagocytosismentioning

confidence: 99%

Magnetic Resonance Imaging and Positron Emission Tomography Approaches to Imaging Vascular and Cardiac Inflammation

Amsallem

Saito

Tada

et al. 2016

Circ J

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Inflammation plays a significant role in a wide range of cardiovascular diseases (CVDs). The numerous implications of inflammation in all steps of CVDs, including initiation, progression and complications, have prompted the emergence of noninvasive imaging modalities as diagnostic, prognostic and monitoring tools. In this review, we first synthesize the existing evidence on the role of inflammation in vascular and cardiac diseases, in order to identify the main targets used in noninvasive imaging. We chose to focus on positron emission tomographic (PET) and magnetic resonance imaging (MRI) studies, which offer the greatest potential of translation and clinical application. We detail the main preclinical and clinical studies in the following CVDs: coronary and vascular atherosclerosis, abdominal aortic aneurysms, myocardial infarction, myocarditis, and acute heart transplant rejection. We highlight the potential complementary roles of these imaging modalities, which are currently being studied in the emerging technology of PET/MRI. Finally, we provide a perspective on innovations and future applications of noninvasive imaging of cardiovascular inflammation. (Circ J 2016; 80: 1269 -1277

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Human ferritin cages for imaging vascular macrophages

Cited by 109 publications

References 39 publications

Bio-inspired protein–gold nanoconstruct with core–void–shell structure: beyond a chemo drug carrier

Bio-inspired protein–gold nanoconstruct with core–void–shell structure: beyond a chemo drug carrier

Dual-Modality Activity-Based Probes as Molecular Imaging Agents for Vascular Inflammation

Magnetic Resonance Imaging and Positron Emission Tomography Approaches to Imaging Vascular and Cardiac Inflammation

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