Engineered ferritin nanocages as natural contrast agents in magnetic resonance imaging

Nandwana, Vikas; Ryoo, Soo‐Ryoon; Kanthala, Shanthi; Kumar, Arvind; Sharma, Ajay; Castro, Fernando C.; Li, Y.; Hoffman, Brian M.; Lim, Sierin; Dravid, Vinayak P.

doi:10.1039/c7ra05681h

Cited by 22 publications

(20 citation statements)

References 50 publications

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“…The isolated plasmid was then transformed into a E. coli BL21(DE3)-C+RIL strain and overexpressed in lysogeny broth (LB) medium containing ampicillin (100 μg/mL) and chloramphenicol (50 μg/mL). The overexpression and protein purification was performed as previously described [16,19]. Optical density (OD) measurements were taken during cell growth.…”

Section: Afftnaa Modification and Productionmentioning

confidence: 99%

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Cyclodextrin conjugated ferritin nanocages reduce intracellular cholesterol level in foam cells

Ravishankar

Lim

2019

Nano Res.

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Accumulation of lipid-laden macrophages (foam cells) is characteristic of atherosclerosis development in the arterial walls. Ferritin nanocages have been found to passively accumulate in the atherosclerotic plaque. Ferritin has been actively investigated as a carrier for contrast agents in atherosclerosis diagnosis. We demonstrate the potential of ferritin as a carrier for therapeutic molecules to mediate cholesterol reduction from foam cells. Cyclodextrin molecules are chemically conjugated to the ferritin nanocages surface or encapsulated within the nanocages using metal co-loading methods. The cyclodextrin-conjugated ferritin has nanomolar affinity to cholesterol molecules. Treatment of foam cells with the conjugates shows decreased levels of intracellular accumulated cholesterol. The preferential localization of ferritin to foam cells is due to transferrin receptor-mediated endocytosis process. These findings show that ferritin nanocages as carriers localize cyclodextrin molecules to foam cells which mediate intracellular cholesterol reduction, thus highlighting its potential use as a therapeutic agent.

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Section: Afftnaa Modification and Productionmentioning

confidence: 99%

“…They subsequently localize in the interstitial space following enhanced permeability and retention (EPR) effects [14,15]. Ferritin has been previously proposed to be used as potential candidate for diagnostic imaging with properties desired for magnetic resonance imaging (MRI) contrast agents [15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Cyclodextrin conjugated ferritin nanocages reduce intracellular cholesterol level in foam cells

Ravishankar

Lim

2019

Nano Res.

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“…These nanoparticles are functionalized through covalent linkage to bind with recombinant L-PGDS which has an affinity to the aggregated amyloids in AD brain. Binding of the L-PGDS to the nanoparticles can indeed enhance their assimilation into the brain regions [18] [19][20][21]. A general protocol for the preparation of stable iron oxide nanoparticles involving the decomposition of the iron-oleate complex at high temperatures is reported elsewhere [22].…”

Section: Resultsmentioning

confidence: 99%

Conjugates of neuroprotective chaperone L-PGDS provide MRI contrast for detection of amyloid β-rich regions in live Alzheimer’s Disease mouse model brain

Sharma¹,

Grandjean²,

Phillips³

et al. 2020

Preprint

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Endogenous brain proteins can recognize the toxic oligomers of amyloid-β (Aβ) peptides implicated in Alzheimer's disease (AD) and interact with them to prevent their aggregation.Lipocalin-type Prostaglandin D Synthase (L-PGDS) is a major Aβ-chaperone protein in the human cerebrospinal fluid. Here we demonstrate that L-PGDS detects amyloids in diseased mouse brain. Conjugation of L-PGDS with magnetic nanoparticles enhanced the contrast for magnetic resonance imaging. We conjugated the L-PGDS protein with ferritin nanocages to detect amyloids in the AD mouse model brain. We show here that the conjugates administered through intraventricular injections co-localize with amyloids in the mouse brain.These conjugates can target the brain regions through non-invasive intranasal administration, as shown in healthy mice. These conjugates can inhibit the aggregation of amyloids in vitro and show potential neuroprotective function by breaking down the mature amyloid fibrils.

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“…This MFt provided a good template for modification, which could be used as a contrast agent in MRI. The superparamagnetic core enhanced contrast enhancement for MRI, without cytotoxicity, and induction of reactive oxygen species [89]. MFts were well-dispersed, non-interacting due to its protein shell.…”

Section: Biomedical Applicationsmentioning

confidence: 99%

Magnetoferritin: Process, Prospects, and Their Biomedical Applications

Xue

Deng

Sun

2019

IJMS

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Ferritin is a spherical iron storage protein composed of 24 subunits and an iron core. Using biomimetic mineralization, magnetic iron oxide can be synthesized in the cavity of ferritin to form magnetoferritin (MFt). MFt, also known as a superparamagnetic protein, is a novel magnetic nanomaterial with good biocompatibility and flexibility for biomedical applications. Recently, it has been demonstrated that MFt had tumor targetability and a peroxidase-like catalytic activity. Thus, MFt, with its many unique properties, provides a powerful platform for tumor diagnosis and therapy. In this review, we discuss the biomimetic synthesis and biomedical applications of MFt.

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Engineered ferritin nanocages as natural contrast agents in magnetic resonance imaging

Abstract: We report the development of a self-assembling protein nanocage as a contrast agent for magnetic resonance imaging (MRI). The protein nanocage is derived from genetically engineered ferritin from

Cited by 22 publications

References 50 publications

Cyclodextrin conjugated ferritin nanocages reduce intracellular cholesterol level in foam cells

Cyclodextrin conjugated ferritin nanocages reduce intracellular cholesterol level in foam cells

Conjugates of neuroprotective chaperone L-PGDS provide MRI contrast for detection of amyloid β-rich regions in live Alzheimer’s Disease mouse model brain

Magnetoferritin: Process, Prospects, and Their Biomedical Applications

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