Xenon-based molecular sensors in lipid suspensions

Meldrum, Tyler; Schröder, Leif; Denger, Philipp; Wemmer, David E.; Pines, Alexander

doi:10.1016/j.jmr.2010.05.005

Cited by 37 publications

(39 citation statements)

References 23 publications

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“…Meldrum et al discovered that cryptophane associated with a dilute suspension of sub-micron Intralipid vesicles yielded a 129 Xe NMR peak that was shifted ~10 ppm downfield from the aqueous 129 Xe-cryptophane peak; 42 similar results were later obtained with different lipid compositions. 43 Most recently, Klippel et al performed hp 129 Xe chemical exchange saturation transfer (Hyper-CEST) NMR spectroscopy and imaging studies in cells loaded with lipophilic cryptophane and found a similar 9-11 ppm downfield chemical shift change, likely due to membrane association.…”

Section: Introductionmentioning

confidence: 78%

A “Smart” ¹²⁹Xe NMR Biosensor for pH-Dependent Cell Labeling

2015

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Here we present a “smart” xenon-129 NMR biosensor that undergoes a peptide conformational change and labels cancer cells at acidic pH. To a cryptophane host molecule with high Xe affinity, we conjugated a 30mer EALA-repeat peptide that is alpha-helical at pH 5.5 and disordered at pH 7.5. The 129Xe NMR chemical shift at rt was strongly pH-dependent (Δδ = 3.4 ppm): δ = 64.2 ppm at pH 7.5 vs. δ = 67.6 ppm at pH 5.5 where Trp(peptide)-cryptophane interactions were evidenced by Trp fluorescence quenching. Using Hyper-CEST NMR, we probed peptido-cryptophane detection limits at low-picomolar (10−11 M) concentration, which compares favourably to other NMR pH sensors at 10−2−10−3 M. Finally, in biosensor-HeLa cell solutions, peptide-cell membrane insertion at pH 5.5 generated a 13.4 ppm downfield cryptophane-129Xe NMR chemical shift relative to pH 7.5 studies. This highlights new uses for 129Xe as an ultrasensitive probe of peptide structure and function, along with potential applications for pH-dependent cell labeling in cancer diagnosis and treatment.

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Section: Introductionmentioning

confidence: 78%

A “Smart” ¹²⁹Xe NMR Biosensor for pH-Dependent Cell Labeling

2015

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“…This differs from results obtained with a less water-soluble dicarboxylic acid cryptophane, which was shown recently to partition from water into suspensions of Intralipid ® vesicles. 45 …”

Section: Resultsmentioning

confidence: 99%

Cell-compatible, integrin-targeted cryptophane-129XeNMR biosensors

et al. 2011

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Peptide-modified cryptophane enables sensitive detection of protein analytes using hyperpolarized 129Xe NMR spectroscopy. Here we report improved targeting and delivery of cryptophane to cells expressing αvβ3 integrin receptor, which is overexpressed in many human cancers. Cryptophane was functionalized with cyclic RGDyK peptide and Alexa Fluor 488 dye, and cellular internalization was monitored by confocal laser scanning microscopy. Competitive blocking assays confirmed cryptophane endocytosis through an αvβ3 integrin receptor-mediated pathway. The peptide–cryptophane conjugate was determined to be nontoxic in normal human lung fibroblasts by MTT assay at the micromolar cryptophane concentrations typically used for hyperpolarized 129Xe NMR biosensing experiments. Flow cytometry revealed 4-fold higher cellular internalization in cancer cells overexpressing the integrin receptor compared to normal cells. Nanomolar inhibitory concentrations (IC50 = 20–30 nM) were measured for cryptophane biosensors against vitronectin binding to αvβ3 integrin and fibrinogen binding to αIIbβ3 integrin. Functionalization of the conjugate with two propionic acid groups improved water solubility for hyperpolarized 129Xe NMR spectroscopic studies, which revealed a single resonance at 67 ppm for the 129Xe-cryptophane–cyclic RGDyK biosensor. Introduction of αIIbβ3 integrin receptor in detergent solution generated a new “bound” 129Xe biosensor peak that was shifted 4 ppm downfield from the “free” 129Xe biosensor.

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“…10 ppm downfield shift for Xe in membrane-associated CrA. [157] This property proved primarily useful to identify cell-associated cages in the first live-cell experiments. [150, 156a] A closer look in combination with FRET data revealed partitioning coefficients on the order 10 2 –10 3 for different membrane compositions.…”

Section: 129xe Cages and Hyper-cest Mrimentioning

confidence: 99%

NMR Hyperpolarization Techniques of Gases

Barskiy

Coffey

Nikolaou

et al. 2016

Chemistry A European J

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157

117

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Nuclear spin polarization can be significantly increased through the process of hyperpolarization, leading to an increase in the sensitivity of nuclear magnetic resonance (NMR) experiments by 4–8 orders of magnitude. Hyperpolarized gases, unlike liquids and solids, can be more readily separated and purified from the compounds used to mediate the hyperpolarization processes. These pure hyperpolarized gases enabled many novel MRI applications including the visualization of void spaces, imaging of lung function, and remote detection. Additionally, hyperpolarized gases can be dissolved in liquids and can be used as sensitive molecular probes and reporters. This mini-review covers the fundamentals of the preparation of hyperpolarized gases and focuses on selected applications of interest to biomedicine and materials science.

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Xenon-based molecular sensors in lipid suspensions

Cited by 37 publications

References 23 publications

A “Smart” ¹²⁹Xe NMR Biosensor for pH-Dependent Cell Labeling

A “Smart” ¹²⁹Xe NMR Biosensor for pH-Dependent Cell Labeling

Cell-compatible, integrin-targeted cryptophane-129XeNMR biosensors

NMR Hyperpolarization Techniques of Gases

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Xenon-based molecular sensors in lipid suspensions

Cited by 37 publications

References 23 publications

A “Smart” 129Xe NMR Biosensor for pH-Dependent Cell Labeling

A “Smart” 129Xe NMR Biosensor for pH-Dependent Cell Labeling

Cell-compatible, integrin-targeted cryptophane-129XeNMR biosensors

NMR Hyperpolarization Techniques of Gases

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Product

Resources

About

A “Smart” ¹²⁹Xe NMR Biosensor for pH-Dependent Cell Labeling

A “Smart” ¹²⁹Xe NMR Biosensor for pH-Dependent Cell Labeling