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In the last 20 years, research in the field of MRI (magnetic resonance imaging) contrast agents (CAs) has been intensified due to the emergence of a disease called nephrogenic systemic fibrosis (NSF). NSF has been linked to the in vivo dissociation of certain Gd(III)-based compounds applied in MRI as CAs. To prevent the dechelation of the probes after intravenous injection, the improvement of their in vivo stability is highly desired. The inertness of the Gd(III) chelates can be increased through the rigidification of the ligand structure. One of the potential ligands is (2,2′,2′′,2′′′-(([2,2′-bipyridine]-6,6′-diylbis(methylene))bis(azanetriyl))tetraacetic acid) (H4DIPTA), which has been successfully used as a fluorescent probe for lanthanides; however, it has never been considered as a potential chelator for Gd(III) ions. In this paper, we report the thermodynamic, kinetic and structural features of the complex formed between Gd(III) and DIPTA. Since the solubility of the [Gd(DIPTA)]− chelate is very low under acidic conditions, hampering its thermodynamic characterization, we can only assume that its stability is close to that determined for the structural analogue [Gd(FENTA)]− (H4FENTA: (1,10-phenanthroline-2,9-diyl)bis(methyliminodiacetic acid)), which is similar to that determined for the agent [Gd(DTPA)]2− routinely used in clinical practice. Unfortunately, the inertness of [Gd(DIPTA)]− is significantly lower (t1/2 = 1.34 h) than that observed for [Gd(EGTA)]− and [Gd(DTPA)]2− as a result of its spontaneous dissociation pathway during dechelation. The relaxivity values of [Gd(DIPTA)]− are comparable with those of [Gd(FENTA)]− and somewhat higher than the values characterizing [Gd(DTPA)]2−. Luminescence lifetime measurements indicate the presence of one water molecule (q = 1) in the inner sphere of the complex with a relatively high water exchange rate (k298ex = 43(5) × 106 s−1). DFT calculations suggest a rigid distorted tricapped trigonal prismatic polyhedron for the Gd(III) complex. On the basis of these results, we can conclude that the bipyridine backbone is not favourable with respect to the inertness of the chelate. [ABSTRACT FROM AUTHOR]

Persistent luminescent nanoparticles (PLNPs) are excellent luminescent materials, and near-infrared PLNPs are efficiently applied for biosensing and bioimaging due to their advantages of no excitation, excellent light stability and long afterglow. However, due to interference from the complex environment within organisms, single-mode imaging methods often face limitations in selectivity, sensitivity, and accuracy. Therefore, it is desirable to construct a dual-mode imaging probe strategy with higher specificity and sensitivity for bioimaging. Magnetic resonance imaging (MRI) has been widely used in the field of bioimaging due to its advantages of high resolution, non-radiation and non-invasiveness. Here, by combining near-infrared PLNPs and manganese dioxide (MnO2) nanosheets, a sensitive and convenient dual-mode "turn on" bioimaging nanoprobe ZGC@MnO2 has been developed for long afterglow imaging and MRI of endogenous hydrogen peroxide (H2O2) in the tumor microenvironment (TME). The monitoring of H2O2 has garnered significant attention due to its crucial role in human pathologies. For the dual-mode "turn on" bioimaging nanoprobe, the near-infrared PLNPs of quasi-spherical ZnGa2O4:Cr (ZGC) nanoparticles were synthesized as luminophores, and MnO2 nanosheets were utilized as a fluorescence quencher, carrier and H2O2 recognizer. H2O2 in the TME could reduce MnO2 nanosheets to Mn2+ for MRI, and ZGC nanoparticles were released for long afterglow imaging. Finally, the ZGC@MnO2 nanoprobe exhibited a rapid response, an excellent signal-to-noise ratio and a limit of detection of 3.67 nM for endogenous H2O2 in the TME. This dual-mode approach enhances the detection sensitivity for endogenous H2O2, thereby facilitating the research of endogenous H2O2-associated diseases and clinical diagnostics. [ABSTRACT FROM AUTHOR]

DaltonTransactions An international journal of inorganic chemistry rsc. li/ dalton Volume 53 Number 22 14 June 2024 Pages 9227- 9598 ISSN 1477- 9226 PAPER Jan Kotek et al. Transition metal complexes of the ( 2,2,2- trifl uoroethyl) phosphinate NOTA analogue as potential contrast agents for 19 F magnetic resonance imaging [Extracted from the article]

A new hexadentate 1,4,7-triazacyclononane-based ligand bearing three coordinating methylene-(2,2,2-trifluoroethyl)phosphinate pendant arms was synthesized and its coordination behaviour towards selected divalent (Mg2+, Ca2+, Mn2+, Fe2+, Co2+, Ni2+, Cu2+, Zn2+) and trivalent (Cr3+, Fe3+, Co3+) transition metal ions was studied. The ligand forms stable complexes with late divalent transition metal ions (from Co2+ to Zn2+) and the complexes of these metal ions are formed above pH ∼3. A number of complexes with divalent metal ions were structurally characterized by means of single-crystal X-ray diffraction. The complex of the larger Mn2+ ion adopts a twisted trigonally antiprismatic geometry with a larger coordination cavity and smaller torsion of the pendant arms, whereas the smaller ions Ni2+, Cu2+ and Zn2+ form octahedral species with a smaller cavity and larger pendant arm torsion. In the case of the Co2+ complexes, both coordination arrangements were observed. The complexes with paramagnetic metal ions were studied from the point of view of potential utilization in 19F magnetic resonance imaging. A significant shortening of the 19F NMR longitudinal relaxation times was observed: a sub-millisecond range for complexes of Cr3+, Mn2+ and Fe3+ with symmetric electronic states (t2g3 and HS-d5), the millisecond range for the Ni2+ and Cu2+ complexes and tens of milliseconds for the Co2+ complex. Such short relaxation times are consistent with a short distance between the paramagnetic metal ion and the fluorine atoms (∼5.5–6.5 Å). Among the redox-active complexes (Mn3+/Mn2+, Fe3+/Fe2+, Co3+/Co2+, Cu2+/Cu+), the cobalt complexes show sufficient stability and a paramagnetic–diamagnetic changeover with the redox potential lying in a physiologically relevant range. Thus, the Co3+/Co2+ complex pair can be potentially used as a smart redox-responsive contrast agent for 19F MRI. [ABSTRACT FROM AUTHOR]

Manganese-based nanomaterials have attracted great interest in cancer nanotheranostics owing to their excellent physicochemical properties. Herein, we report α-phase manganese sulfide nanotheranostics (MnSN) as an MRI-guided chemodynamic therapy agent and cGAS-STING agonist for tumor immunotherapy. MnSN can degrade into manganese ions in response to the mildly acidic tumor microenvironment. This unique feature endows MnSN with the ability to produce sufficient hydroxyl radicals (˙OH) and achieve efficient chemodynamic therapy in vitro and vivo. More importantly, the released manganese ions successfully activate the cGAS-STING pathway, resulting in the significant immune effect and inhibiting the tumor metastasis. Besides, the pH-responsive degradation endows MnSN with activable T1 magnetic resonance imaging to monitor the treatment progress. This study demonstrates that MnSN holds great potential for the precise diagnosis and inhibition of tumor growth and metastasis. [ABSTRACT FROM AUTHOR]

It is still a big challenge to design Gd3+ based nanoparticles (NPs) for T1 MRI (Magnetic Resonance Imaging) with high performance and clarify the effects of relative time parameters on longitudinal relaxivity r1. In this paper, we simulated the influences of different time parameters on the longitudinal relaxivity of Gd3+ based NPs with inner-sphere and outer-sphere theories, respectively. In particular, we investigated the effects of τR (the rotational time), τM (the residence time), Tie (the electronic relation time) and τd (the diffusion time) on longitudinal relaxivity. In the relaxation process of Gd3+ based NPs, the inner-sphere plays a dominant role, in which τR and τM have a greater impact on r1. Based on the simulation results, we proposed a design strategy of Gd3+ based NPs for T1 MRI, which focuses on the rational decrease of hydrated radius, and the optimal range of the hydrated radius is about 0.8–2.5 nm. In addition, we synthesized ultrasmall Gd2O3 NPs with a hydrated radius of about 2.5 nm, which have a high longitudinal relaxivity r1 of 10.8 mM−1 s−1 at 3.0 T. Moreover, the in vivo imaging results confirm that the ultrasmall Gd2O3 NPs have a good imaging effect on the tumor, and it can be a good candidate as a T1 MRI contrast agent with high performance. [ABSTRACT FROM AUTHOR]

High-spin Fe(III) complexes of 1,4,7-triazacyclononane (TACN) with mixed oxygen donor pendants including hydroxypropyl, phenolate or amide groups are prepared for study as T1 MRI probes. Complexes with two hydroxypropyl pendants and either amide (Fe(TOAB)) or phenolate (Fe(PTOB)) groups are compared to an analog with three hydroxypropyl groups (Fe(NOHP)), in order to study the effect of the third pendant on the coordination sphere as probed by solution chemistry, relaxivity and structural studies. Solution studies show that Fe(PTOB) has two ionizations with the phenol pendant deprotonating with a pKa of 1.7 and a hydroxypropyl pendent with pKa of 6.3. The X-ray crystal structure of [Fe(PTOB)]Br2 features a six-coordinate complex with two bound hydroxypropyl groups, and a phenolate in a distorted octahedral geometry. The Fe(TOAB) complex has a single deprotonation, assigned to a hydroxypropyl group with a pKa value of 7.0. Both complexes are stabilized as high-spin Fe(III) in solution as shown by their effective magnetic moments and Fe(III)/Fe(II) redox potentials of −390 mV and −780 mV versus NHE at pH 7 and 25 °C for Fe(TOAB) and Fe(PTOB) respectively. Both Fe(PTOB) and Fe(TOAB) are kinetically inert to dissociation under a variety of challenges including phosphate/carbonate buffer, one equivalent of ZnCl2, two equivalents of transferrin or 100 mM HCl, or at basic pH values over 24 h at 37 °C. The r1 relaxivity of Fe(TOAB) at 1.4 T, pH 7.4 and 33 °C is relatively low at 0.6 mM−1 s−1 whereas the r1 relaxivity of Fe(PTOB) is more substantial and shows an increase of 2.5 fold to 2.5 mM−1 s−1 at acidic pH. The increase in relaxivity at acidic pH is attributed to protonation of the phenolate group to provide an additional pathway for proton relaxation. [ABSTRACT FROM AUTHOR]

With the rapid development of nanotechnology and biomedicine, numerous gadolinium (Gd)-based nanoparticle MRI contrast agents have been widely investigated. Due to the unique physicochemical properties of nanoparticles and the complexity of biological systems, the biosafety of Gd-based nanoparticle MRI contrast agents has been paid more and more attention. Herein, for the first time, we employed an ultra-high performance liquid chromatography–electrospray ionization quadrupole time-of-flight/mass spectrometry (UPLC-ESI-QTOF/MS)-based metabolomics approach to investigate the potential toxicity of Gd-based nanoparticle MRI contrast agents. In this work, NaGdF4 and PEG-NaGdF4 nanoparticles were successfully constructed and selected as the representative Gd-based nanoparticle MRI contrast agents for the metabolomics analysis. Based on the results of metabolomics, more metabolic biomarkers and pathways were identified in the NaGdF4 group than those in the PEG-NaGdF4 group. Careful analysis of these metabolic biomarkers and pathways suggested that NaGdF4 nanoparticles induced disturbance of pyrimidine and purine metabolism, inflammatory response, and kidney injury to a certain extent compared with PEG-NaGdF4 nanoparticles. These results indicated that Gd-based nanoparticle contrast agents modified with PEG had better biosafety. Additionally, it was demonstrated that the discovery of characteristic metabolomics biomarkers induced by nanoparticles would provide a new approach for biosafety assessment and stimulate the development of nanomedicine. [ABSTRACT FROM AUTHOR]

Transition-metal dichalcogenides (TMDCs) have attracted a lot of attention due to their electronic, optical, mechanical, and catalytic properties. In addition, TMDCs possess rich redox chemistry that enables the decoration of metal nanoparticles directly on their surfaces. In this paper, MnO2/MoS2 nanocomplexes were obtained by the spontaneous reduction of KMnO4 with MoS2 QDs as the reductive agent. The formed MnO2/MoS2 nanocomplexes exhibited activated fluorescence and MR imaging signal in the presence of glutathione (GSH). After conjugation with an AS1411 aptamer, specific in vivo MR imaging and fluorescence labeling of the 786-O tumor cells were realized, showing their promising potential for biomedical applications. [ABSTRACT FROM AUTHOR]

Chemodynamic therapy (CDT), as a reactive oxygen species (ROS)-based therapeutic modality, has attracted much attention in recent years. However, the insufficient therapeutic effect of CDT is due to the antioxidant system in the tumor microenvironment, such as high levels of glutathione (GSH). In this study, we developed a biological/physical dual-targeting nanotheranostic agent (relaxation rate, r1: 6.3 mM−1 s−1 and r2: 13.11 mM−1 s−1) for enhanced CDT of SMCC-7721 tumors. This nanotheranostic agent is composed of a homologous tumor cell membrane (TCM), magnetic ferric oxide, and manganese oxide and is denoted as FM@TCM nanoparticles (NPs). A favorable effect of in vitro CDT on SMCC-7721 cells (IC50: 20 μg mL−1) is demonstrated, attributed to the Fenton reaction and oxidative stress resulting from the reduction of the GSH level. In vivo T1/T2 magnetic resonance imaging (MRI) confirms that the tumor accumulation of FM@TCM NPs is promoted by concurrent bioactive targeting of the homologous TCM and physico-magnetic targeting of tumor tissues with an external magnetic field. Impressive chemodynamic therapeutic effects on SMCC-7721 tumors are demonstrated through the catalysis of endogenous hydrogen peroxide and depletion of GSH to generate high levels of ROS. Dual-targeting FM@TCM NPs inhibit SMCC-7721 tumor growth (∼90.9%) in vivo without any biotoxicity. This nanotheranostic agent has great potential for use in MRI-guided CDT. [ABSTRACT FROM AUTHOR]

Co(II) and Ni(II) complexes of two tri-pyridine-based ligands with two hydroxy and two amide exchangeable protons (TDTA) and with six amide exchangeable protons (TMTP) were investigated for application as paraCEST-based magnetic resonance imaging (MRI) contrast agents. The two hydroxy groups present in the TDTA ligand were found to be passive while the amide group was active towards the CEST process. In the case of the Co(II) and Ni(II) complexes of the TMTP ligand, all three coordinated amide groups participated in the exchange process, and excellent CEST signals were observed. The X-ray structure of the four complexes revealed the seven-coordinate geometry of Co(II) complexes and the six-coordinate geometry of Ni(II) complexes. The presence of amide protons and hydroxy protons in the complexes was detected by the NMR method. The stability of the complexes in solution at high temperatures, in different pH ranges and acidic conditions, in the presence of competing cations, and biologically relevant anions was investigated. Potentiometric titrations were carried out to determine the ligand's protonation constants and the complexes' thermodynamic stability constant at 25.0 °C and I = 0.15 mol L-1 NaClO4. ParaCEST studies of [Co(TMTP)]2+ and [Ni(TMTP)]2+ at variable pH and variable pulse power are highlighted. [ABSTRACT FROM AUTHOR]

A new cyclam-based ligand bearing two methylene(2,2,2-trifluoroethyl)phosphinate pendant arms was synthesized and its coordination behaviour towards selected divalent transition metal ions [Co(II), Ni(II), Cu(II), Zn(II)] was studied. The ligand was found to be very selective for the Cu(II) ion according to the common Williams–Irving trend. Complexes with all the studied metal ions were structurally characterized. The Cu(II) ion forms two isomeric complexes; the pentacoordinated isomer pc-[Cu(L)] is the kinetic product and the octahedral trans-O,O′-[Cu(L)] isomer is the final (thermodynamic) product of the complexation reaction. Other studied metal ions form octahedral cis-O,O′-[M(L)] complexes. The complexes with paramagnetic metal ions showed a significant shortening of 19F NMR longitudinal relaxation times (T1) to the millisecond range [Ni(II) and Cu(II) complexes] or tens of milliseconds [Co(II) complex] at the temperature and magnetic field relevant for 19F magnetic resonance imaging (MRI). Such a short T1 results from a short distance between the paramagnetic metal ion and the fluorine atoms (∼6.1–6.4 Å). The complexes show high kinetic inertness towards acid-assisted dissociation; in particular, the trans-O,O′-[Cu(L)] complex was found to be extremely inert with a dissociation half-time of 2.8 h in 1 M HCl at 90 °C. Together with the short relaxation time, it potentially enables in vitro/in vivo utilization of the complexes as efficient contrast agents for 19F MRI. [ABSTRACT FROM AUTHOR]

Lanthanide clusters with good stability and intriguing physical properties are attractive in many fields. By reacting 9-anthracenylphosphonic acid (AnPO3H2) and lanthanide nitrates under solvothermal conditions, we obtained a series of hexanuclear lanthanide phosphonate cages [H3O][Ln6(PO4)(AnPO3)8(DMF)6]·2DMF·H2O (Ln6, Ln = NdIII, EuIII, GdIII, DyIII, HoIII, ErIII, YbIII). Within the cluster, the six Ln atoms form an octahedron and its eight faces are covered by phosphonate groups. The in situ generated phosphate anion resides inside the cage and binds to the six Ln atoms via its four oxygen atoms. Photoluminescence studies show that Nd6, Er6 and Yb6 can emit near-infrared (NIR) luminescence due to the energy transfer from the anthracene ligand to the lanthanide ions. Magnetic studies reveal the magnetocaloric effect of Gd6 with an entropy change (−ΔSm) of 25.92 J kg−1 K−1 at 2.5 K and ΔH = 0–7 T. The possibility of using Gd6 as a contrast agent for magnetic resonance imaging was also explored with longitudinal (r1) and transverse (r2) relaxivities of 5.68 mM−1 s−1 per Gd and 158.11 mM−1 s−1 per Gd, respectively. [ABSTRACT FROM AUTHOR]

Magnetic resonance imaging was employed for the first time to visualize the gravity sedimentation of kaolin suspensions, allowing the internal spatial distribution of kaolin during sedimentation to be investigated. This revealed very complex behaviours dependent on the initial kaolin concentration and solution pH, including vertical channelling, curved channelling, layers/voids and voids only. We show that the number of channels formed increases with the solution pH, with the channels distributed in an evenly spaced-out pattern. The discovery of spontaneous and very stable "void" spaces within the suspension is similar to that previously reported in charged gases (plasmas) and in suspensions of charged Latex particles, which have been explained by the presence of many-body attractive forces. The discovery of such spontaneous voids occurring during kaolin sedimentation, may provide a fundamental explanation for the formation of water channels. [ABSTRACT FROM AUTHOR]

Two zinc finger peptides, namely ZFQDLn and ZFQELn (Ln = Tb or Gd), with an appended Ln3+ chelate and a phosphoserine able to coordinate the Ln3+ ion are presented. The two peptides differ by the amino acid anchorage of the chelate, either aspartate (D) or glutamate (E). Both peptides are able to bind Zn2+ and adopt the ββα fold. Interestingly, ZFQETb shows a decrease in sensitized Tb3+ luminescence upon Zn2+ binding whereas ZFQDTb does not. The luminescence change upon Zn2+ binding is attributed to a change in hydration number (q) of the Tb3+ ion due to the decoordination of the phosphoserine from the Ln3+ ion upon Zn2+ binding and peptide folding. This process is highly sensitive to the length of the linker between the Ln chelate and the peptidic backbone. The magnetic properties of the gadolinium analogue ZFQEGd were studied. An impressive relaxivity increase of 140% is observed at 60 MHz and 25 °C upon Zn2+ binding. These changes can be attributed to a combined increase effect of the hydration number of Gd3+ and of the rigidity of the system upon Zn2+ binding. Phantom MR images at 9.4 T show a clear signal enhancement in the presence of Zn2+. These zinc finger peptides offer a unique platform to design such Zn-responsive probes. [ABSTRACT FROM AUTHOR]

In the current work, hollow Fe3O4@Au hybrid nanoparticles (h-NPs) with a size of 17 nm were synthesised through seeded growth and galvanic replacement reactions. The influence of the experimental parameters such as the reaction time and precursor concentration on the formation of h-NPs was investigated. The hydrophobic hollow Fe3O4@Au h-NPs were transferred into water by coating with an amphiphilic polymer, poly(maleic anhydride-alt-1-octadecene) (PMAO), to form highly stable colloids. The PMAO coated hollow Fe3O4@Au h-NPs provide an excellent signal enhancement of T1- and T2-weighted MRI (r1 = 8.47 mM−1 s−1, r2 = 74.45 mM−1 s−1). Magnetic and photothermal data of the hollow Fe3O4@Au h-NPs indicated that sample temperature can reach 70 °C under a magnetic field of 16 kA m−1 and a frequency of 450 kHz for 2 min and 808 nm NIR laser at a power density of 0.65 W cm−2 for 2 min. This effective combination between the magnetic thermia of the magnetic cores and the photothermal effect of the gold shell indicates hollow Fe3O4@Au h-NPs as a potential material for efficient cancer theranostics. [ABSTRACT FROM AUTHOR]

A series of Cu(II) complexes with cyclam-based ligands containing two N-(2,2,2-trifluoroethyl)-aminoalkyl pendant arms in 1,8-positions (L1: 1,2-ethylene spacer, L2: 1,3-propylene spacer; L3: 1,4-butylene spacer) was studied in respect to potential use as contrast agents for 19F magnetic resonance imaging (MRI). A number of structures of the complexes as well as of several organic precursors were determined by single-crystal X-ray diffraction analysis. Geometric parameters (especially distances between fluorine atoms and the central metal ion) were determined for each complex and the identity of isomeric complex species present in solution was established. The NMR longitudinal relaxation times (T1) of 19F nuclei in the ligands at clinically relevant fields and temperatures (1–2 s) were significantly shortened upon Cu(II) binding to 7–10 ms for [Cu(L1)]2+, 20–30 ms for [Cu(L2)]2+ and 20–50 ms for [Cu(L3)]2+. The trend of the relaxation time shortening is in accordance with the distance and number of chemical bonds between fluorine atoms and the Cu(II) ion. The signals show promising T2*/T1 ratios in the range 0.25–0.55, assuring their good applicability to 19F NMR/MRI. The results show that even the Cu(II) ion, with a small magnetic moment, causes significant relaxation enhancement with a long-range effect and can be considered as a highly suitable metal ion for efficient 19F MRI contrast agents. [ABSTRACT FROM AUTHOR]

This document is a back cover advertisement for Dalton Transactions, an international journal of inorganic chemistry. It promotes professional recognition and career advancement in the field of science. The advertisement encourages readers to apply for professional registers or chartered status to gain recognition and inspire confidence and trust. It also mentions a research article by Kosuke Kitase et al. showcasing research from Professor Kitazawa's laboratory at Toho University in Japan. The article discusses the synthesis of a novel Soma-Iwamoto-type complex with spin-crossover properties. Additionally, the document mentions another research article by Jan Kotek et al. on transition metal complexes as potential contrast agents for 19F magnetic resonance imaging. [Extracted from the article]

Contrast-agent enhanced magnetic resonance imaging (MRI) has been under continuous investigation for the conspicuous imaging of lesions and the early-stage detection of tumors. To achieve the development of a T1-weighted contrast agent with a high relaxivity value, herein, porous silica nanoparticles that had internalized about 20 aquated cationic Gd(III) complexes (1) of the hexadentate hydroxyethyl-appended picolinate-based ligand H2hbda were demonstrated. Complex 1 exhibited a longitudinal relaxivity value per mM Gd(III) ions, r1, of 9.05 mM−1 s−1 (pH 7.4, 37 °C, 1.41 T), which increased to 86.41 mM−1 s−1 because of the grafting of complex 1 in the inner core of porous silica nanospheres through electrostatic interactions between the anionic silica surface and the cationic complex 1 molecules. A further augmentation in the relaxivity value to 118.32 mM−1 s−1 was realized because of the interaction of the complex 1@SiO2NPs with serum albumin protein. The synthesized nanosystem was impervious to physiologically available anions (HPO42− and HCO31−) and also kinetically inert, as evidenced via a transmetallation experiment in the presence of Zn(II) ions. The developed complex-incorporated nanomaterial was bio- and hemo-compatible. Cellular uptake measurements employing HeLa cells and the concentration-dependent enhancement in the brightness of in vitro phantom images, recorded under a clinical scanner at 1.5 T, demonstrated that the developed biocompatible 1@SiO2NP complex has promising diagnostic applications as a T1-weighted MRI contrast agent. [ABSTRACT FROM AUTHOR]

Carbon quantum dots (CQDs) with good biosafety can be doped with metals to construct multimodal imaging probes with a wide range of applications in fluorescence and molecular imaging. However, developing CQDs with both long-wavelength emission and a variety of imaging modes remains a challenge. In this article, novel bismuth- and gadolinium-codoped carbon quantum dots (Bi,Gd-CQDs) were developed using a hydrothermal method for green and red fluorescence imaging, X-ray computed tomography (CT) imaging, and T1-weighted magnetic resonance imaging (T1-weighted MRI). In addition to exceptional water solubility, strong steady fluorescence characteristics, and great biocompatibility, the obtained Bi,Gd-CQDs have a high X-ray attenuation coefficient and a short magnetic resonance T1 relaxation time. Additionally, cell imaging involved red fluorescence imaging with deep penetration. Therefore, the prepared Bi,Gd-CQDs with green and red dual-emissions can be used as nanoprobes for fluorescence, CT, and T1-weighted MR imaging, expanding their application prospects in the field of biomedicine. [ABSTRACT FROM AUTHOR]

With the extensive usage of gadolinium-based contrast agents (GBCAs) in magnetic resonance imaging (MRI), gadolinium deposition has been observed in the brain, kidneys, liver, etc., and this is also closely related to the development of nephrogenic systemic fibrosis (NSF) in patients with renal dysfunction. Chelation, thereby promoting the elimination of deposited Gd(III), seems to be promising for alleviating these problems. Despite many ligands suitable for chelation therapy having been studied, the decorporation of transition metals (e.g. iron, copper, lead, etc.) and actinides (e.g. uranium, plutonium, etc.) has long been a primary concern, whereas the study of Gd(III) has been extremely limited. Due to their excellent metal binding abilities in vivo and therapeutic effects toward neurodegenerative diseases, bidentate hydroxypyridinone ligands are expected to be able to remove Gd(III) from the brain, kidneys, bones, and liver. Herein, the Gd(III) decorporation efficacy of a bidentate hydroxypyridinone ligand (Me-3,2-HOPO) has been evaluated. The complexation behavior between Me-3,2-HOPO and Gd(III) in solution and solid states was characterized with the assistance of potentiometric titration and X-ray diffraction techniques, respectively. Solution-based thermodynamic studies illustrate that the dominant species of complex between Gd(III) and Me-3,2-HOPO (HL) is GdL2+ (log β120 = 11.8 (3)) at pH 7.4. The structure of the Gd–Me-3,2-HOPO crystal obtained from a room temperature reaction reveals the formation of a Gd(III) dimer that is chelated by four ligands as a result of metal ion hydration and ligand complexation. Cellular Gd(III) removal assays illustrate that Me-3,2-HOPO could effectively reduce final amounts of gadolinium by 77.6% and 66.1% from rat renal proximal tubular epithelial (NRK-52E) cells and alpha mouse liver 12 (AML-12) cells, respectively. Our current results suggest the potential of bidentate HOPO ligands as an effective approach to treat patients suffering from Gd(III) toxicity. [ABSTRACT FROM AUTHOR]

As human blood is 90% water, aqueous solubility is key for any drug that is designed for in vivo applications. Good water solubility reduces the dose and makes a drug safer, and exogenous MRI contrast agents are no different. In particular, the efficiency of chemical exchange saturation transfer (CEST)-based MRI contrast agents depends largely on how well they mix with water. Several compounds in spite of containing exchangeable protons do not exhibit CEST contrast due to poor water solubility. In this work, we explore the possibility of carbon quantum dot formation through hydrothermal treatment as a solubility-improvement method for such prospective MRI contrast agents. We report a proof of principle study by demonstrating how a poorly-water-soluble amino-thioamide compound shows a post-treatment improvement in solubility and consequently a several-fold enhancement in the CEST contrast efficiency. [ABSTRACT FROM AUTHOR]

Gadolinium (Gd)-based magnetic resonance imaging (MRI) contrasting agents interfere with the determination of selenium (Se) when analysed by single quadrupole inductively coupled plasma-mass spectrometry (ICP-MS). This paper demonstrates that an ICP-triple quadrupole-MS (ICP-QQQ-MS) with oxygen mass shift overcomes Gd++ interference on Se+ and mitigates typically encountered matrix and spectral based interferences. Normal human serum was diluted in a solution containing isopropanol, EDTA, NH4OH and Triton X-100. Samples were unspiked (control) serum; serum spiked with 0.127 μmol L−1 Se or 127 μmol L−1 Gd; and serum spiked with both 0.127 μmol L−1 Se and 127 μmol L−1 Gd. Consideration of collision/reaction gases and conditions for interference mitigation included helium (He); a ‘low’ and ‘high’ hydrogen (H2) flow, and oxygen (O2). The instrument tune for O2 was optimised for effective elimination of interferences via a mass shift reaction of Se+ to SeO+. The ICP-QQQ-MS was capable of detecting trace (＞9.34 nmol L−1) levels of Se in serum in the presence of Gd in our simulated post-MRI serum sample. The multi-tune capabilities of the ICP-QQQ-MS may be adapted to eliminate other specific isobaric interferences that cause false positive results in other analyses where the analyte is confounded by doubly charged and/or polyatomic species. [ABSTRACT FROM AUTHOR]

The development of metal-based multimodal imaging probes is a highly challenging field in coordination chemistry. In this context, we have developed a bifunctional hexadentate tripodal ligand (H3L2) with three 3,4-HOPO moieties attached to a flexible tetrahedral carbon bearing a functionalizable nitro group. Complexes formed with different metal ions have potential interest for diagnostic applications, namely magnetic resonance imaging (MRI) and positron emission tomography (PET). The capacity of the ligand to coordinate GdIII and GaIII was studied and the thermodynamic stability constants of the respective complexes were determined by potentiometry and spectrophotometry. The ligand forms stable 1 : 1 ML complexes though with considerably higher affinity for GaIII than for GdIII (pGa = 26.2 and pGd = 14.3 at pH 7). The molecular dynamics simulations of the GdIII complex indicate that two water molecules can coordinate the metal ion, thus providing efficient paramagnetic enhancement of water proton relaxation. The relaxation and the water exchange properties of the GdIII chelate, assessed by a combined 17O NMR and 1H NMRD study, showed associative activated water exchange with a relatively low rate constant, k 298ex = (0.82 ± 0.11) × 107 s−1, and some aggregation tendency. Biodistribution studies of the 67Ga-L2 complex suggested good in vivo stability and quick renal clearance. Further anchoring of this ligand with specific biotargeting moieties might open future prospectives for applications of labelled conjugates in both MRI and 68Ga-PET diagnostic imaging. [ABSTRACT FROM AUTHOR]

Metal phosphides have been proved to be potential theranostic agents of tumors. However, the limitations of single-modal imaging or the treatment effect of such materials need to be further improved. Here, we successfully prepared polyvinylpyrrolidone-modified bimetallic nickel cobalt phosphide (NiCoP/PVP) nanoparticles as a theranostic agent of tumors. Owing to the different types of magnetic properties of Ni and Co components, T1- and T2-weighted magnetic resonance imaging (MRI) could be simultaneously achieved to compensate the low accuracy brought about by single-modal MRI. In addition, NiCoP/PVP possesses excellent photothermal properties owing to its obvious absorption in the near-infrared (NIR) region, which endows NiCoP/PVP with high photothermal conversion efficiency (PCE) to serve as a photothermal agent for tumor ablation. Therefore, NiCoP/PVP is a promising theranostic agent for accurate diagnosis and effective treatment of tumors. [ABSTRACT FROM AUTHOR]

Biofilms are comprised of microbial cells and an extracellular polymeric substance (EPS) matrix that supports interactions between community members and with the local environment. The highly hydrated EPS matrix makes the application of many biofilm visualization techniques difficult. Hence, to better visualize how biofilms interact with their environment, there is a need for imaging techniques to monitor hydrated state biofilm dynamics. We employed an in situ dynamic approach to construct label-free images of biofilms. In situ imaging was conducted using a vacuum compatible microfluidic reactor, SALVI (System for Analysis at the Liquid Vacuum Interface), for biofilm growth; real-time confocal laser scanning microscopy analysis; and nuclear magnetic resonance (NMR) microimaging and spectroscopy. We integrated SALVI microchannel fluids and live biofilms to demonstrate in situ measurement capabilities, including velocity mapping, diffusion coefficient mapping, relaxometry, localized spectroscopy, UGRAPHIC DISPLAY="INLINE" ID="UGT1" SRC="UGT1"/ relaxation times, porosity, and two- and three-dimensional imaging within the microchannel at high spatial resolution. We monitored organic acids adjacent to biofilms, suggesting that kinetic rate and substrate-product yield ratio studies are possible using the SALVI microfluidic reactor for growth characterizations. The integration of NMR microimaging studies into the SALVI platform demonstrates that a multimodal microfluidic platform can serve as an avenue to explore complex biological phenomena, such as biofilm attachment to surfaces, with detailed quantitative physical and chemical mapping. The further incorporation of other SALVI-compatible technologies, such as liquid time-of-flight secondary ion mass spectrometry imaging, with NMR microimaging will produce a powerful correlative approach to monitor in situ biofilm chemistry and dynamics at different spatial scales. [ABSTRACT FROM AUTHOR]

Dual-modal lanthanide-doped gadolinium nanoparticles (NPs), which exhibit an excellent magnetic resonance imaging (MRI) spatial resolution and high fluorescence imaging (FI) sensitivity, have attracted tremendous attention in biotechnology and nanomedicine applications. In this paper, terbium (Tb) ion doped gadolinium oxide (Gd2O3:Tb) NPs with varied Tb concentrations were synthesized by a laser ablation in liquid (LAL) method. The characterization of the structure, morphology, and composition shows that these NPs are spherical with excellent crystallinity. The effects of Tb ion concentration on the visible green fluorescence and longitudinal relaxivity were investigated, indicating that the fluorescence properties were significantly influenced by the Tb ion concentration, but all samples were still efficient T1-weighted contrast agents. Furthermore, the optimum Tb doping concentration was determined to be 1%. The cell viability, cellular fluorescence imaging and in vivo MRI of this dual-modal nano-probe were studied, with the results revealing that the Gd2O3:Tb NPs did not have a significant cytotoxic effect, making them good candidates for use as a dual-modal contrast agent for MRI and fluorescence imaging.

A multifunctional supramolecular complex is reported for the integrated multiple magnetic resonance imaging/computed X-ray tomography (MRI/CT) imaging and photothermal therapy, wherein a gadolinium-substituted paramagnetic polyoxometalate cluster and food-borne antioxidant peptides identified from the trepang protein hydrolysates are introduced. The as-prepared complex maintained an uniform particle size and much better biocompatibility, and is an ideal candidate for the in vivo applications. The complex allows for T1-weighted MR imaging and a high Hounsfield unit value for enhanced CT imaging. Interestingly, we demonstrate that the complex possesses outstanding photothermal cancer-killing effects due to its high photothermal conversion efficiency under the exposure of an NIR laser and enhanced antibacterial activity to avoid bacterial infection from the thermal therapeutic process. These results indicate that the supramolecular complex platform exhibit potential for accurate medical diagnosis at an early stage and effective eradication of the tumor cells. [ABSTRACT FROM AUTHOR]

We report a series of structurally related Gd(III) complexes designed to modulate the exchange of the coordinated water molecule, which is an important parameter to be controlled to achieve optimal performance of contrast agents for application in magnetic resonance imaging (MRI). The ligands contain a DO3A scafold functionalised with 2′-methoxyphenacyl or 4′-methoxyphenacyl groups (DO3A-oMAP and DO3A-pMAP), a 2′-aminophenacyl group (DO3A-oAnAP) or a 2′,4′-dihydroxyphenacyl moiety (DO3A-DiHAP). The results are compared with those obtained previously for the analogues containing 2′- or 4′-hydroxyphenacyl groups (DO3A-oHAP and DO3A-pHAP, respectively) and the parent system with an unsubstituted acetophenone pendant arm (DO3A-AP). 1H NMR studies performed on the Eu(III) complexes show that ligand functionalisation causes a very minor effect on the relative populations of the SAP and TSAP isomers present in solution, with the SAP isomer representing 70–80% of the overall population. The emission spectra of the Eu(III) complexes confirm the presence of a water molecule coordinated to the metal center and point to similar coordination environments around the metal ion. The analysis of the 1H NMRD profiles and 17O NMR data recorded for the Gd(III) complexes evidences that water exchange is modulated by the ability of peripherical substituents to establish hydrogen bonds with the coordinated and/or second sphere water molecules. DFT calculations were used to model the transition states responsible for the dissociative water exchange mechanism, providing support to the crucial role of hydrogen-bonds in accelerating water exchange. [ABSTRACT FROM AUTHOR]

Gd-based contrast agents (GBCAs) are frequently administered to patients for magnetic resonance imaging to enhance tissue contrasts. After examination, they are excreted and enter surface waters via local wastewater treatment plants' effluents where they lead to anthropogenic Gd anomalies in the environment of metropolitan areas with developed healthcare. This work presents the speciation analysis of GBCAs in water samples from Australia by targeting individual GBCAs in effluent, river and seawater samples obtained from New South Wales (Sydney area), the Northern Territory (Alice Springs) and Victoria (Melbourne area). A method based on hydrophilic interaction liquid chromatography (HILIC) coupled to inductively coupled plasma-mass spectrometry (ICP-MS) provided rapid separation and quantification of four common GBCAs in under three minutes. To improve the sensitivity, ion extraction and transport processes were optimised and the quadrupole mass filter was operated with an increased mass bandpass, decreasing limits of detection to between 18 and 24 ng L−1 for individual GBCAs. This allowed detection of Gd-DOTA, Gd-BT-DO3A and Gd-DTPA-BMA at concentrations of up to 160 ng L−1 in water samples collected from rivers within the proximity of effluents of local wastewater treatment plants. The analysis of GBCAs in oceanic sea water required the development of a novel automated micro-solid phase extraction (μSPE) method for matrix elimination and analyte pre-concentration enabling the detection of Gd-DOTA and Gd-BT-DO3A. [ABSTRACT FROM AUTHOR]

The high porosity and versatile structures of metal–organic frameworks (MOFs) as new theranostic platforms have drawn broad attention and have been widely explored. This has inspired the use of MOFs to encapsulate various functional nanoparticles within the frameworks to further develop and extend the biomedical applications in drug delivery and bioimaging. Herein, we fabricated yolk–shell magnetic composites Fe3O4@Co/Zn-ZIF towards magnetic resonance (MR) imaging-guided chemotherapy by combining a controlled encapsulation process with a mild phase transformation under solvothermal conditions. The designed yolk–shell composites Fe3O4@Co/Zn-ZIF exhibited high doxorubicin (DOX) loading capacity, pH-responsive release characteristics, good biocompatibility and strong T2-weighted MR imaging contrast enhancement. The hollow structure Co/Zn-ZIF serving as a shell could collapse under low pH conditions, and achieved controlled release of drugs. Dopamine-modified Fe3O4 nanoparticles (Fe3O4–DA NPs) as the core could confer Fe3O4@Co/Zn-ZIF with outstanding MR imaging capacity and facile magnetic separation. This strategy sheds light on a new way to develop multifunctional drug delivery systems by using hollow structures of MOFs as hosts for different functional nanoparticles. [ABSTRACT FROM AUTHOR]

New pyridine containing triAza; 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene-3,6,9-triacetic acid (PCTA) ligands presenting pendant carboxylic acid or alcohol functions have been synthesized and used to form diaqua Gd(III) complexes, which have been immobilized onto dense silica nanoparticles. Cytotoxicity studies of these complexes (free or immobilized on the nanoparticles) on normal 1BR3G cells and cancerous HCT 116 cells indicated a dependence on the pendant chemical group for the free complexes. However, this effect disappeared once the complexes were immobilized on the surface of the nanoparticles, leading to non-toxic nanomaterials. The interest of these complexes (free or immobilized on dense silica nanoparticles) as contrast agents in magnetic resonance imaging (MRI) has been evaluated in comparison with DOTAREM® by recording their nuclear magnetic resonance dispersion (NMRD) profiles, measuring their transversal and longitudinal relaxivities as well as recording images on phantoms at 37 °C. This study has evidenced the high potential of these complexes: first it suggested the possibility to reduce the dose to be injected by a factor of 10, second it evidenced their high efficiency in high field T1-weighted MRI (9.4 T), the key towards images of higher resolution and shorter acquisition times. [ABSTRACT FROM AUTHOR]

Signal amplification by reversible exchange (SABRE), a parahydrogen-based hyperpolarization technique, is valuable in detecting low concentrations of chemical compounds, which facilitates the understanding of their functions at the molecular level as well as their applicability in nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI). SABRE of 1-aminoisoquinoline (1-AIQ) is significant because isoquinoline derivatives are the fundamental structures in compounds with notable biological activity and are basic organic building blocks. Through this study, we explain how SABRE is applied to hyperpolarize 1-AIQ for diverse solvent systems such as deuterated and non-deuterated solvents. We observed the amplification of individual protons of 1-AIQ at various magnetic fields. Further, we describe the polarization transfer mechanism of 1-AIQ compared to pyridine using density functional theory (DFT) calculations. This hyperpolarization technique, including the polarization transfer mechanism investigation on 1-AIQ, will provide a firm basis for the future application of the hyperpolarization study on various bio-friendly materials. [ABSTRACT FROM AUTHOR]

The article presents abstracts on inorganic chemistry which include the metal ions in medical imaging, the use of photophysical properties in bioassays and cellular optical imaging and the magnetic resonance imaging (MRI) probe.

Gd3+ and Tm3+ doped Prussian blue (Gd/Tm–PB) with high uniformity and dispersibility was synthesized by a facile solvothermal method. The conditions for the synthesis of Gd/Tm–PB were explored. Through the regulation of the ratio of Gd3+/Tm3+, the Gd/Tm–PB particles with the optimal size (about 150–200 nm) and the best fluorescence and photothermal effect were obtained. On the basis of the optimal Gd/Tm–PB, further coated by polydopamine (PDA) functionalized metal–organic frameworks (MOFs), a multifunctional platform Gd/Tm–PB@ZIF-8/PDA for cancer diagnosis and treatment was established. Doxorubicin (DOX) was selected as a drug model and the drug loading of Gd/Tm–PB@ZIF-8/PDA was found to be 81 mg g−1. Cytotoxicity analysis indicated that Gd/Tm–PB@ZIF-8/PDA was highly biocompatible. The DOX release at different pH values and GSH concentrations revealed an excellent pH/GSH-triggered drug release. Through the combination of the near infrared photothermal performance of Gd/Tm–PB, chemo-photothermal therapy can be achieved to further improve the anti-cancer efficiency. In addition, the Gd/Tm–PB@ZIF-8/PDA nanoparticles can be tracked by fluorescence imaging (FOI) and magnetic resonance imaging (MRI). Cell FOI and in vivo MRI experiments showed the potential application of Gd/Tm–PB@ZIF-8/PDA in dual mode imaging guided therapy. In vivo antitumor experiments demonstrated the higher anticancer efficacy of Gd/Tm–PB@ZIF-8/PDA with a combined effect of chemo-photothermal therapy. This work provides a new strategy for nano-drug carriers in the direction of integrated diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Gadolinium(III) complexes are generally considered efficient magnetic resonance imaging (MRI) contrast agents (CAs) and widely used in clinical applications. High relaxivity and stability are two essential criteria for a Gd(III)-complex to be used as a MRI-CA. One crucial strategy to achieve high relaxivity for small molecular Gd(III)-based MRI contrast agents is to increase the hydration number q. Meanwhile, metal complexes with macrocyclic ligands have been proved to inherit high thermodynamic stability and kinetic inertness. Herein, a series of macrocyclic ligands based on diethylenetriamine-N-oxide pentaacetic acid-bisamide were synthesized. Among them, cyclo-DTPA-NO-C6O2 (3d) was the strongest ligand for Gd(III) as confirmed by experimental results. The hydration number of the Gd-cyclo-DTPA-NO-C6O2 (4d) complex was characterized by luminescence measurements to be 3 and the coordination structure was confirmed with computational simulations. Consequently, the relaxivity of this complex (14.3 mM−1 s−1, 1.5 T, 25 °C) is about triple that of commercial MRI CAs. The conditional stability constant of the Gd(III) complex, pGd, calculated from spectrophotometric titration studies, was comparable to that of one of the most stable commercial MRI-CAs, Gd-DTPA (Magnevist®). Meanwhile, the kinetic inertness of the complex was even higher than that of Gd-DTPA thanks to its macrocyclic coordination structure. [ABSTRACT FROM AUTHOR]

In recent years, carbon dots (CDs) with red-emitting wavelengths have received increasing attention in cancer therapy and imaging. Here, we reported a multi-functional CD based platform combining bimodal magnetic resonance/fluorescence (MR/FL) imaging and chemodynamic therapy (CDT) for in vivo imaging of tumor tissues and efficient anticancer treatment. The red-emitting CDs were synthesized via a one-step solvothermal method with p-phenylenediamine as the carbon source. Ethylenediaminetetraacetic acid (EDTA) was covalently coupled to the surface of CDs and then complexed with Fe2+ and Gd3+ to obtain functionalized red CDs (CDs@EDTA@Gd@Fe). CDs@EDTA@Gd@Fe exhibited bright and stable fluorescence and strong T1-weighted MR imaging (MRI) contrast. Moreover, the CDs@EDTA@Gd@Fe showed an excellent anticancer effect both in vitro and in vivo via a Fenton reaction-based CDT by releasing Fe2+ in the tumor. Our study offers a promising strategy for developing multi-functional CDs for cancer theranostics. [ABSTRACT FROM AUTHOR]

Heat therapy is a promising therapeutic modality for cancer treatment due to the minimum adverse effects of selective local hyperthermia; however, the low heating efficiency of heat therapy under safe conditions is an issue for its bioapplication. Here, we report the synthesis of water-dispersible sulfur doped iron oxides (SDIOs) with different phase structures and the exploration of the relationships between the different SDIOs and their induction heating capacities as a guideline to obtain a photo-magnetic hyperthermia agent. The agent exhibits good biocompatibility, excellent photothermal conversion efficiency (55.8%) and great T2 weighted magnetic resonance imaging (63.7 mM−1 s−1). Significantly, the SDIOs effectively eliminate tumours in a biologically safe AC magnetic field range (H·f = 4.3 < 5.0 × 106 kA m−1 s−1) and with 808 nm laser irradiation at a safe density of 0.33 W cm−2; also, they can be mostly metabolized from the body after one month. The work presented here adopts anion-doped iron oxides to dramatically improve photo-magnetic hyperthermia effects and may enable further exploration in thermotherapeutic research. [ABSTRACT FROM AUTHOR]

Laser vaporisation is a promising technology for the industrial manufacturing of spherical, oxidic nanoparticles, including crystalline, less-agglomerated ferromagnetic maghemite (γ-Fe2O3) and superparamagnetic γ-Fe2O3/amorphous SiO2 composite nanoparticles. These can be utilised in medical applications such as contrast agents in magnetic resonance imaging (MRI) and may replace common contrast agents such as gadolinium chelate complexes. Nano-specific risk assessment and life cycle assessment have been used in parallel in order to critically assess benefits and shortcomings of this technological approach and to find the key parameters for process optimisation. Potential risks in occupational safety were found to be low, but the energy demand of the laser system is crucial in terms of environmental impact potential. However, process optimisation options in process efficiency, laser source and reuse of waste heat were identified, leading to a decrease of the overall cumulated energy demand up to 94%. Flame spray pyrolysis was included in the comparative study as an alternative approach for gas phase synthesis of oxidic nanoparticles. Both technologies and the resulting nanoenabled products were found to be environmentally beneficial compared to the preparation of the standard MRI contrast agent Gadovist®. [ABSTRACT FROM AUTHOR]

Paramagnetic polyoxometalates [RE30Co8Ge12W108O408(OH)42(OH2)30]56− (Rare Earth (RE): Gd, Dy, Eu, and Y) are of special interest with regard to their application as alternative contrast agents in non-human magnetic resonance imaging which is increasingly used in materials science and process engineering. This class of new paramagnetic materials promises detailed findings in the magnetic resonance images due to their rather large total electron spin on the one hand, i.e. large, field-dependent relaxivities up to the highest magnetic fields, and due to their relatively large cluster sizes with an impact on adsorption and penetration on the other hand. Apart from the magnetic field dependence, the sensitivity of relaxivities to motional correlation times will be shown for these polyoxometalates which is a prerequisite for modelling and understanding the physical behaviour of this new class of polyoxometalates in MRI. Also for the qualitative and quantitative interpretation of MR images, the knowledge of transverse and longitudinal relaxivities of the paramagnetic clusters in a given environment is mandatory. Examples considered in this publication are proteins in milk fractionation, the deposit of which was measured by MRI. [ABSTRACT FROM AUTHOR]

Understanding the relationship between chemical structure and the effectiveness of bioresponsive magnetic resonance imaging (MRI) contrast agents can offer help to identify key components required for the future development of such probes. Here, we report the development and characterisation of two novel monomeric bifunctional chelators, L1 and L2, whose paramagnetic metal complexes can serve as calcium-responsive contrast agents. Specifically, relaxometric titrations, luminescence lifetime measurements, high resolution NMR and diffusion experiments, as well as density functional theory (DFT) calculations were carried out to assess the behaviour of each system. Minor structural differences between the probes resulted from the extension of the linker between the macrocyclic lanthanide chelator and the acyclic Ca-binding moiety. Relaxometric titrations of both systems, GdL1 and GdL2, showed an increase in r1 and r2 relaxivity upon Ca2+ addition, with the derivative bearing the longer linker showing a greater overall change. The hydration states of the europium analogues were assessed revealing a higher initial hydration state for EuL2. Diffusion ordered NMR spectroscopy revealed negligible changes in the diffusive properties of both systems upon the addition of Ca2+, while NMR studies of the Y3+, Yb3+ and Eu3+ analogues provided further insights into the structural behaviour of the linker unit in both the unsaturated and Ca-saturated states. DFT calculations supported the different coordination modes of the studied paramagnetic complexes in the presence and absence of Ca2+. Overall, our findings demonstrate the impact of subtle changes to the structure of such probes, affecting a range of properties and their coordination behaviour. [ABSTRACT FROM AUTHOR]

In order to unravel the relationship between zeta potential values and r2/r1 ratios for contrast agents in MRI application, a series of macroporous Prussian blue cubes were successfully synthesized by HCl etching and used as model samples for relaxivity investigation. It was found that their r2/r1 ratios firstly decreased and then increased with the increasing HCl concentration, while the variation trend for zeta potential is quite the opposite. By employing Gauss fitting and eliminating the HCl concentration in the resultant equations, a relationship between zeta potential values and r2/r1 ratios, i.e. ζ = 229 × (563 −r2/r1)0.012− 267, was finally obtained. This result showed that magnetic resonance imaging relaxivities (viz. r2/r1) could be tailored through altering zeta potential values (surface charges) of the contrast agent. [ABSTRACT FROM AUTHOR]

The challenging diagnosis and differentiation between multiple sclerosis and amyotrophic lateral sclerosis relies on the clinical assessment of the symptoms along with magnetic resonance imaging and sampling cerebrospinal fluid for the search of biomarkers for either disease. Despite the progress made in imaging techniques and biomarker identification, misdiagnosis still occurs. Here we used 2.5 μL of serum samples to obtain the infrared spectroscopic signatures of sera of multiple sclerosis and amyotrophic lateral sclerosis patients and compared them to those of healthy controls. The spectra are then classified with the help of a two-fold Random Forest cross-validation algorithm. This approach shows that infrared spectroscopy is powerful in discriminating between the two diseases and healthy controls by offering high specificity for multiple sclerosis (100%) and amyotrophic lateral sclerosis (98%). In addition, data after six and twelve months of treatment of the multiple sclerosis patients with biotin are discussed. [ABSTRACT FROM AUTHOR]

We reported a set of water-soluble transition metal complexes that can serve as both 19F and PARACEST magnetic resonance imaging agents. The high number of equivalent fluorine atoms and the paramagnetic effect of metals offer these complexes high 19F sensitivity as demonstrated by in vitro19F MRI experiments. The complexes contain carboxamide groups appended onto a cyclen macrocycle, which provide 1H CEST peaks well differentiated from bulk water. The Co(ii) agent displays two CEST peaks that can be utilized for ratiometric pH determination and the concept of combining 19F MR and PARACEST as complementary imaging techniques was demonstrated with the Fe(ii) complex. [ABSTRACT FROM AUTHOR]

Magnetic hyperthermia and magnetic resonance imaging (MRI) are two of the most important biomedical applications of magnetic nanoparticles (MNPs). However, the design of MNPs with good heating performance for hyperthermia and dual T1/T2 contrast for MRI remains a considerable challenge. In this work, ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs) are synthesized through a simple one-step methodology. A post-synthetic purification strategy has been implemented in order to separate discrete nanoparticles from aggregates and unstable nanoparticles, leading to USPIONs that preserve chemical and colloidal stability for extended periods of time. The optimized nanoparticles exhibit high saturation magnetization and show good heating efficiency in magnetic hyperthermia experiments. Remarkably, the evaluation of the USPIONs as MRI contrast agents revealed that the nanoparticles are also able to provide significant dual T1/T2 signal enhancement. These promising results demonstrate that USPIONs are excellent candidates for the development of theranostic nanodevices with potential application in both hyperthermia and dual T1/T2 MR imaging. [ABSTRACT FROM AUTHOR]