Cellular labeling with Gd(III) chelates: only high thermodynamic stabilities prevent the cells acting as ‘sponges’ of Gd3+ ions

Cabella, Claudia; Crich, Simonetta Geninatti; Corpillo, Davide; Barge, Alessandro; Ghirelli, Cristina; Bruno, E.; Lorusso, Vito; Uggeri, Fulvio; Aime, Silvio

doi:10.1002/cmmi.88

Cited by 97 publications

(90 citation statements)

References 25 publications

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“…This indicates that a significant amount of Tb(III) is dissociated from the complex at the cell surface, which is in agreement with the known relatively low kinetic stability of Gd-DTPA-bisamide complexes. Previously, poor stability of another Gd-complex of a DTPA-bisamide, Gd-DTPA-BMA, was observed in cell experiments [57].…”

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confidence: 98%

Glycoconjugate Probes and Targets for Molecular Imaging Using Magnetic Resonance

2010

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Review Molecular recognition of sugar residues applied in molecular imagingMolecular imaging aims at probing the molecular abnormalities that are the basis of diseases rather than to image their effects [1]. An important prerequisite of this approach is the selection of appropriate markers of disease and of targeting vectors to recognize them. The latter can include low-molecular weight substrates for enzymes or high-molecular weight affinity ligands, such as monoclonal antibodies, hormone analogs and recombinant proteins. Of the three major classes of biomolecules (proteins, nucleic acids and carbohydrates), the latter class is the least exploited in molecular imaging. However, a dense layer of glyco conjugates covers all cells and carbohydrate mediated cellular recognition plays an important role in nature, both in normal and malignant processes, such as cell-cell communication, infection, inflammation, metastasis and reproduction. As carriers of information, the carbohydrates have far greater potential than proteins and nucleic acids; three different nucleotides or amino acids can generate only six distinguishable structures, while over 1000 structures can be built up from three different monosaccharides [2]. This level of complexity is probably the reason for the fact that the exploration of these compounds in molecular imaging is lagging behind [3]. Recently, significant progress has been made in glycochemistry and glycobiology; for example, automated solid-phase synthesis of oligo saccharides has become possible [4], carbohydrate-based vaccines have been developed [5] and high-throughput methods have been designed for the screening of molecular interactions [6]. The exciting new developments in glycoscience are opening way for new challenges in exploring the full potential of carbohydrates in molecular imaging. Therefore, here we give an overview of the recent literature on the use of glycoconjugates either as probes or targets in molecular imaging using MRI.MRI contrast agents (CAs) are broadly described as positive or negative, depending on whether they give rise to a brightening or a darkening effect on the MR image, respectively. The positive or brightening effect predominantly relates to the longitudinal proton relaxation time (T 1 ) and the negative or darkening effect predominantly relates to the transverse proton relaxation time (T 2 ). To date, the majority of commercially available and clinically applied positive CAs are Gd 3+ complexes of the polyaminocarboxylates diethylene triamine pentacetic acid (DTPA) and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) (see FiguRe 1 for some typical examples) and negative CAs are various iron oxide particles. These agents are not actively targeting. The targeted CAs for application in molecular imaging that are currently under development and described below are generally based on compounds 1 (Gd-DTPA) and 2 (Gd-DOTA), as well as iron oxide nanoparticles.Glycoconjugate probes and targets for molecular imaging using magnetic resonanceRecently...

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confidence: 98%

Glycoconjugate Probes and Targets for Molecular Imaging Using Magnetic Resonance

2010

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“…The encapsulation of Gd-DOTP complex was determined relaxometrically after acid mineralization of the suspension [33].…”

Section: Encapsulation Efficiency Of Plp and Gd-dotp In Theranostic Nmentioning

confidence: 99%

Preparation and in vitro characterization of chitosan nanobubbles as theranostic agents

Cavalli

Argenziano

Vigna

et al. 2015

Colloids and Surfaces B: Biointerfaces

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Please cite this article as: R. Cavalli, M. Argenziano, E. Vigna, P. Giustetto, E. Torres, S. Aime, E. Terreno, Preparation and in vitro characterization of chitosan nanobubbles as theranostic agents, Colloids and Surfaces B: Biointerfaces (2015), http://dx.doi.org/10. 1016/j.colsurfb.2015.03.023 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.Page 1 of 27 A c c e p t e d M a n u s c r i p A c c e p t e d M a n u s c r i p t 2 ABSTRACT Theranostic delivery systems are nanostructures that combine the modality of therapy and diagnostic imaging. Polymeric micro-and nanobubbles, spherical vesicles containing a gas core, have been proposed as new theranostic carriers for MRI-guided therapy. In this study, chitosan nanobubbles were purposely tuned for the co-delivery of prednisolone phosphate and a Gd (III) complex, as therapeutic and MRI diagnostic agent, respectively. Perfluoropentane was used for filling up the internal core of the formulation. These theranostic nanobubbles showed diameters of about 500 nm and a positive surface charge that allows the interaction with the negatively charged Gd-DOTP complex. Pluronic F68 was added to the nanobubble aqueous suspension as stabilizer agent. The encapsulation efficiency was good for both the active compounds, and a prolonged drug release profile was observed in vitro. The effect of ultrasound stimulation on prednisolone phosphate release was evaluated at 37 °C. A marked increase on drug release kinetics with no burst effect was obtained after the exposure of the system to ultrasound. Furthermore, the relaxivity of the MRI probe changed upon incorporation in the nanobubble shell, thereby offering interesting opportunity in dual MRI-US experiments. The ultrasound characterization showed a good in vitro echogenicity of the theranostic nanobubbles.In summary, chitosan drug-loaded nanobubbles with Gd (III) complex bound to their shell might be considered a new platform for imaging and drug delivery with the potential of improving anticancer treatments.

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“…In fact, it has been shown that Gd complexes with thermodynamic association constants  10 17 when added to cell incubation media, show net transfer of Gd ions to the cell membrane followed by a slower internalization process. [11]. Figure 1 shows two types of amphiphilic Gd-complexes used to prepare Gd-loaded HDL particles.…”

Section: High Density Lipoproteins (Hdl)mentioning

confidence: 99%

Lipid-Based Nanoparticles in Cardiovascular Molecular Imaging

Crich

Alberti

Orio

et al. 2012

Curr Cardiovasc Imaging Rep

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Abstract.The Gd(III) complexes currently used as MRI contrast agents are hydrophilic agents that distribute in the vascular and extracellular compartments. The visualization of atherosclerotic plaques requires systems endowed with lipophilic characteristics. Several Gd(III) complexes bearing lipophilic substituents have been reported. Among them Gd(III) complexes containing one or two aliphatic chains appears particularly useful for the intended application. These amphiphilic Gd(III) complexes have been incorporated into various type of supramolecular adducts that ensure enough sensibility for their detection in MR images of atherosclerotic plaques. Much attention has been devoted to the use of HDL and LDL Gd-loaded particles. The presence of long aliphatic chain(s) promotes the spontaneous aggregation of these complexes to form micelles that may associate as such to the surface of HDL particles. It has been shown that the transfer of single amphiphilic complexes into the lipidic core of the particles is possible by de-assembling the micelles through the formation of "host-guest" adducts with cyclodextrin. Gd-loaded liposomes have also been successfully tested in plaque detection as well as perfluoronanoparticles loaded with CEST agents. 4Introduction.

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Cellular labeling with Gd(III) chelates: only high thermodynamic stabilities prevent the cells acting as ‘sponges’ of Gd3+ ions

Cited by 97 publications

References 25 publications

Glycoconjugate Probes and Targets for Molecular Imaging Using Magnetic Resonance

Glycoconjugate Probes and Targets for Molecular Imaging Using Magnetic Resonance

Preparation and in vitro characterization of chitosan nanobubbles as theranostic agents

Lipid-Based Nanoparticles in Cardiovascular Molecular Imaging

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