Lanthanide Inorganic Nanoparticles Enhance Semiconducting Polymer Nanoparticles Afterglow Luminescence for In Vivo Afterglow/Magnetic Resonance Imaging.

Dual/multimodal imaging strategies are increasingly recognized for their potential to provide comprehensive diagnostic insights in cancer imaging by harnessing complementary data. This study presents an innovative probe that capitalizes on the synergistic benefits of afterglow luminescence and magnetic resonance imaging (MRI), effectively eliminating autofluorescence interference and delivering a superior signal-to-noise ratio. Additionally, it facilitates deep tissue penetration and enables noninvasive imaging. Despite the advantages, only a limited number of probes have demonstrated the capability to simultaneously enhance afterglow luminescence and achieve high-resolution MRI and afterglow imaging. Herein, we introduce a cutting-edge imaging platform based on semiconducting polymer nanoparticles (PFODBT) integrated with NaYF4@NaGdF4 (Y@Gd@PFO-SPNs), which can directly amplify afterglow luminescence and generate MRI and afterglow signals in tumor tissues. The proposed mechanism involves lanthanide nanoparticles producing singlet oxygen (1O2) upon white light irradiation, which subsequently oxidizes PFODBT, thereby intensifying afterglow luminescence. This innovative platform paves the way for the development of high signal-to-background ratio imaging modalities, promising noninvasive diagnostics for cancer.

Dynamic monitoring soft tissue healing via visualized Gd-crosslinked double network MRI microspheres.

By integrating magnetic resonance-visible components with scaffold materials, hydrogel microspheres (HMs) become visible under magnetic resonance imaging(MRI), allowing for non-invasive, continuous, and dynamic monitoring of the distribution, degradation, and relationship of the HMs with local tissues. However, when these visualization components are physically blended into the HMs, it reduces their relaxation rate and specificity under MRI, weakening the efficacy of real-time dynamic monitoring. To achieve MRI-guided in vivo monitoring of HMs with tissue repair functionality, we utilized airflow control and photo-crosslinking methods to prepare alginate-gelatin-based dual-network hydrogel microspheres (G-AlgMA HMs) using gadolinium ions (Gd (III)), a paramagnetic MRI contrast agent, as the crosslinker. When the network of G-AlgMA HMs degrades, the cleavage of covalent bonds causes the release of Gd (III), continuously altering the arrangement and movement characteristics of surrounding water molecules. This change in local transverse and longitudinal relaxation times results in variations in MRI signal values, thus enabling MRI-guided in vivo monitoring of the HMs. Additionally, in vivo data show that the degradation and release of polypeptide (K2 (SL)6 K2 (KK)) from G-AlgMA HMs promote local vascular regeneration and soft tissue repair. Overall, G-AlgMA HMs enable non-invasive, dynamic in vivo monitoring of biomaterial degradation and tissue regeneration through MRI, which is significant for understanding material degradation mechanisms, evaluating biocompatibility, and optimizing material design.

Development of a separability index for task specific characterization of spectral computed tomography.

PURPOSE: In this work, we define a signal detection based metrology to characterize the separability of two different multi-dimensional signals in spectral CT acquisitions. METHOD: Signal response was modelled as a random process with a deterministic signal and stochastic noise component. A linear Hotelling observer was used to estimate a scalar test statistic distribution that predicts the likelihood of an intensity value belonging to a signal. Two distributions were estimated for two materials of interest and used to derive two metrics separability: a separability index (s') and the area under the curve of the test statistic distributions. Experimental and simulated data of photon-counting CT scanners were used to evaluate each metric. Experimentally, vials of iodine and gadolinium (2, 4, 8 mg/mL) were scanned at multiple tube voltages, tube currents and energy thresholds. Additionally, a simulated dataset with low tube current (10-150 mAs) and material concentrations (0.25-4 mg/mL) was generated. RESULTS: Experimental data showed that conditions favorable for low noise and expression of k-edge signal produced the highest separability. Material concentration had the greatest impact on separability. The simulated data showed that under more difficult separation conditions, difference in material concentration still had the greatest impact on separability. CONCLUSION: The results demonstrate the utility of a task specific metrology to measure the overlap in signal between different materials in spectral CT. Using experimental and simulated data, the separability index was shown to describe the relationship between image formation factors and the signal responses of material.

Pentacenequinone-Modulated 2D GdSn-PQ Nanosheets as a Fluorescent Probe for the Detection of Enrofloxacin in Biological and Environmental Samples.

The fate and effects of fluoroquinolone antibacterial (FQ) on the environment are important since there appears to be a surge in FQ resistance like enrofloxacin (ENR) in both environmental and clinical organisms. Numerous reports indicate that the sensing capabilities of these antibiotics need to be improved. Here, we have investigated the interaction of ENR with our synthesized pentacenequinone-modulated gadolinium-tin (GdSn-PQ) nanosheets and the formation of intermolecular interactions that caused the occurrence of aggregation-induced emission enhancement. The concept for designing hybrid metallic nanosheets comes from the unique features inherited from the parent organic precursor. Due to the distinct interaction between ENR and GdSn-PQ, the interstate conversion (ISC) between GdSn-PQ and ENR induces a significant wavelength shift in photoluminescence (PL), improving reliability, selectivity, and visibility compared to quenching- or AIEE-based methods without peak shifts, allowing for highly sensitive and visually detectable analyses. The fluorescence signal of GdSn-PQ exhibited a linear relationship (R2 = 0.9911), with the added ENR concentrations ranging from 5 to 90 nM, with a detection limit of 0.10 nM. We have demonstrated its potential and wide use in the detection of ENR in biological samples (human urine and blood serum) and environmental samples (tap water and seawater) with a recovery rate of 98- 108%. The current approach has demonstrated that the 2D GdSn-PQ nanosheet is a novel and powerful platform for future biological and environmental studies.

Chiral coordination polymer nanowires boost radiation-induced in situ tumor vaccination.

Radiation-induced in situ tumor vaccination alone is very weak and insufficient to elicit robust antitumor immune responses. In this work, we address this issue by developing chiral vidarabine monophosphate-gadolinium nanowires (aAGd-NWs) through coordination-driven self-assembly. We elucidate the mechanism of aAGd-NW assembly and characterize their distinct features, which include a negative surface charge, ultrafine topography, and right-handed chirality. Additionally, aAGd-NWs not only enhance X-ray deposition but also inhibit DNA repair, thereby enhancing radiation-induced in situ vaccination. Consequently, the in situ vaccination induced by aAGd-NWs sensitizes radiation enhances CD8+ T-cell-dependent antitumor immunity and synergistically potentiates the efficacy immune checkpoint blockade therapies against both primary and metastatic tumors. The well-established aAGd-NWs exhibit exceptional therapeutic capacity and biocompatibility, offering a promising avenue for the development of radioimmunotherapy approaches.

Influence of SPION Surface Coating on Magnetic Properties and Theranostic Profile.

This study aimed to develop multifunctional nanoplatforms for both cancer imaging and therapy using superparamagnetic iron oxide nanoparticles (SPIONs). Two distinct synthetic methods, reduction-precipitation (MR/P) and co-precipitation at controlled pH (MpH), were explored, including the assessment of the coating's influence, namely dextran and gold, on their magnetic properties. These SPIONs were further functionalized with gadolinium to act as dual T1/T2 contrast agents for magnetic resonance imaging (MRI). Parameters such as size, stability, morphology, and magnetic behavior were evaluated by a detailed characterization analysis. To assess their efficacy in imaging and therapy, relaxivity and hyperthermia experiments were performed, respectively. The results revealed that both synthetic methods lead to SPIONs with similar average size, 9 nm. Mössbauer spectroscopy indicated that samples obtained from MR/P consist of approximately 11-13% of Fe present in magnetite, while samples obtained from MpH have higher contents of 33-45%. Despite coating and functionalization, all samples exhibited superparamagnetic behavior at room temperature. Hyperthermia experiments showed increased SAR values with higher magnetic field intensity and frequency. Moreover, the relaxivity studies suggested potential dual T1/T2 contrast agent capabilities for the coated SPpH-Dx-Au-Gd sample, thus demonstrating its potential in cancer diagnosis.

Chiral Pyclen-Based Heptadentate Chelates as Highly Stable MRI Contrast Agents.

In recent years, pyclen-based complexes have attracted a great deal of interest as magnetic resonance imaging (MRI) contrast agents (CAs) and luminescent materials, as well as radiopharmaceuticals. Remarkably, gadopiclenol, a Gd(III) bishydrated complex featuring a pyclen-based heptadentate ligand, received approval as a novel contrast agent for clinical MRI application in 2022. To maximize stability and efficiency, two novel chiral pyclen-based chelators and their complexes were developed in this study. Gd-X-PCTA-2 showed significant enhancements in both thermodynamic and kinetic stabilities compared to those of the achiral parent derivative Gd-PCTA. 1H NMRD profiles reveal that both chiral gadolinium complexes (Gd-X-PCTA-1 and Gd-X-PCTA-2) have a higher relaxivity than Gd-PCTA, while variable-temperature 17O NMR studies show that the two inner-sphere water molecules have distinct residence times τMa and τMb. Furthermore, in vivo imaging demonstrates that Gd-X-PCTA-2 enhances the signal in the heart and kidneys of the mice, and the chiral Gd complexes exhibit the ability to distinguish between tumors and normal tissues in a 4T1 mouse model more efficiently than that of the clinical agent gadobutrol. Biodistribution studies show that Gd-PCTA and Gd-X-PCTA-2 are primarily cleared by a renal pathway, with 24 h residues of Gd-X-PCTA-2 in the liver and kidney being lower than those of Gd-PCTA.

Biochemical and biophysical interaction of rare earth elements with biomacromolecules: A comprehensive review.

The growing utilization of rare earth elements (REEs) in industrial and technological applications has captured global interest, leading to the development of high-performance technologies in medical diagnosis, agriculture, and other electronic industries. This accelerated utilization has also raised human exposure levels, resulting in both favourable and unfavourable impacts. However, the effects of REEs are dependent on their concentration and molecular species. Therefore, scientific interest has increased in investigating the molecular interactions of REEs with biomolecules. In this current review, particular attention was paid to the molecular mechanism of interactions of Lanthanum (La), Cerium (Ce), and Gadolinium (Gd) with biomolecules, and the biological consequences were broadly interpreted. The review involved gathering and evaluating a vast scientific collection which primarily focused on the impact associated with REEs, ranging from earlier reports to recent discoveries, including studies in human and animal models. Thus, understanding the molecular interactions of each element with biomolecules will be highly beneficial in elucidating the consequences of REEs accumulation in the living organisms.

Evaluation of hafnium oxide nanoparticles imaging characteristics as a contrast agent in X-ray computed tomography.

This research aimed to compare the quantitative imaging attributes of synthesized hafnium oxide nanoparticles (NPs) derived from UiO-66-NH2(Hf) and two gadolinium- and iodine-based clinical contrast agents (CAs) using cylindrical phantom. Aqueous solutions of the studied CAs, containing 2.5, 5, and 10 mg/mL of HfO2NPs, gadolinium, and iodine, were prepared. Constructed within a cylindrical phantom, 15 cc small tubes were filled with CAs. Maintaining constant mAs, the phantom underwent scanning at tube voltage variations from 80 to 140 kVp. The CT numbers were quantified in Hounsfield units (HU), and the contrast-to-noise ratios (CNR) were calculated within delineated regions of interest (ROI) for all CAs. The HfO2NPs at 140 kVp and concentration of 2.5 mg/ml exhibited 2.3- and 1.3-times higher CT numbers than iodine and gadolinium, respectively. Notably, gadolinium consistently displayed higher CT numbers than iodine across all exposure techniques and concentrations. At the highest tube potential, the maximum amount of the CAs CT numbers was attained, and at 140 kVp and concentration of 2.5 mg/ml of HfO2NPs the CNR surpassed iodine by 114%, and gadolinium by 30%, respectively. HfO2NPs, as a contrast agent, demonstrated superior image quality in terms of contrast and noise in comparison to iodine- and gadolinium-based contrast media, particularly at higher energies of X-ray in computed tomography. Thus, its utilization is highly recommended in CT.

Remotely controlled drug release in deep brain regions of non-human primates.

Many areas of science and medicine would benefit from selective release of drugs in specific regions. Nanoparticle drug carriers activated by focused ultrasound-remotely applied, depth-penetrating energy-may provide such selective interventions. Here, we developed stable, ultrasound-responsive nanoparticles that can be used to release drugs effectively and safely in non-human primates. The nanoparticles were used to release propofol in deep brain visual regions. The release reversibly modulated the subjects' visual choice behavior and was specific to the targeted region and to the released drug. Gadolinium-enhanced MR imaging suggested an intact blood-brain barrier. Blood draws showed normal clinical chemistry and hematology. In summary, this study provides a safe and effective approach to release drugs on demand in selected deep brain regions at levels sufficient to modulate behavior.

Expression of concern: Gadolinium embedded iron oxide nanoclusters as T1-T2 dual-modal MRI-visible vectors for safe and efficient siRNA delivery.

Expression of concern for 'Gadolinium embedded iron oxide nanoclusters as T1-T2 dual-modal MRI-visible vectors for safe and efficient siRNA delivery' by Xiaoyong Wang et al., Nanoscale, 2013, 5, 8098-8104, https://doi.org/10.1039/C3NR02797J.

A Dual-Gene Reporter-Amplifier Architecture for Enhancing the Sensitivity of Molecular MRI by Water Exchange.

The development of genetic reporters for magnetic resonance imaging (MRI) is essential for investigating biological functions in vivo. However, current MRI reporters have low sensitivity, making it challenging to create significant contrast against the tissue background, especially when only a small fraction of cells express the reporter. To overcome this limitation, we developed an approach for amplifying the sensitivity of molecular MRI by combining a chemogenetic contrast mechanism with a biophysical approach to increase water diffusion through the co-expression of a dual-gene construct comprising an organic anion transporting polypeptide, Oatp1b3, and a water channel, Aqp1. We first show that the expression of Aqp1 amplifies MRI contrast in cultured cells engineered to express Oatp1b3. We demonstrate that the contrast amplification is caused by Aqp1-driven increase in water exchange, which provides the gadolinium ions internalized by Oatp1b3-expressing cells with access to a larger water pool compared with exchange-limited conditions. We further show that our methodology allows cells to be detected using approximately 10-fold lower concentrations of gadolinium than that in the Aqp1-free scenario. Finally, we show that our approach enables the imaging of mixed-cell cultures containing a low fraction of Oatp1b3-labeled cells that are undetectable on the basis of Oatp1b3 expression alone.

[Gd(HB-DO3A)]: Equilibrium, Dissociation Kinetic and Structural Differences in a Simple Homolog of [Gd(HP-DO3A)] (Prohance®).

[Gd(HP-DO3A)] (gadoteridol) as an active compound of ProHance® is a widely employed contrast agent in clinical MRI scans in the last 30 years. Recent concerns about the long-term retention of gadolinium-based contrast agents (GBCAs) led to a deeper investigation of the structural features underlying the integrity of the paramagnetic metal complex. Several human and nonclinical studies have noted marked differences among the macrocyclic GBCAs, with the least retention of Gd traces and most rapid elimination consistently being reported for [Gd(HP-DO3A)]. It was deemed of interest to assess how minor structural/electronic changes associated to the ligand structure may affect basic properties of the metal complex with several [Gd(HP-DO3A)] analogues synthesized and characterized in the last years. We recently reported that the closest homolog of [Gd(HP-DO3A)], i. e.: [Gd(HB-DO3A)], in which a (±)-2-hydroxy-1-propyl pendant arm is replaced by a (±)-2-hydroxy-1-butyl moiety, showed a significantly different retention behaviour in the model interaction with collagen, despite the apparently very minor structural difference. In this paper we report a comprehensive study of the structural, thermodynamic, kinetic and relaxation properties of [Gd(HB-DO3A)], compared to the parent [Gd(HP-DO3A)] and to other closely related macrocyclic GBCAs to assess whether very minor structural changes can modulate the physico-chemical properties of Gd3+ complexes.

Near-infrared-II fluorescence/magnetic resonance double modal imaging of transplanted stem cells using lanthanide co-doped gadolinium oxide nanoparticles.

To ensure maximum therapeutic safety and efficacy of stem cell transplantation, it is essential to observe the kinetics of behavior, accumulation, and engraftment of transplanted stem cells in vivo. However, it is difficult to detect transplanted stem cells with high sensitivity by conventional in vivo imaging technologies. To diagnose the kinetics of transplanted stem cells, we prepared multifunctional nanoparticles, Gd2O3 co-doped with Er3+ and Yb3+ (Gd2O3: Er, Yb-NPs), and developed an in vivo double modal imaging technique with near-infrared-II (NIR-II) fluorescence imaging and magnetic resonance imaging (MRI) of stem cells using Gd2O3: Er, Yb-NPs. Gd2O3: Er, Yb-NPs were transduced into adipose tissue-derived stem cells (ASCs) through a simple incubation process without cytotoxicity under certain concentrations of Gd2O3: Er, Yb-NPs and were found not to affect the morphology of ASCs. ASCs labeled with Gd2O3: Er, Yb-NPs were transplanted subcutaneously onto the backs of mice, and successfully imaged with good contrast using an in vivo NIR-II fluorescence imaging and MRI system. These data suggest that Gd2O3: Er, Yb-NPs may be useful for in vivo double modal imaging with NIR-II fluorescence imaging and MRI of transplanted stem cells.

A Gadolinium(III) Complex Based on Pyridoxine Molecule with Single-Ion Magnet and Magnetic Resonance Imaging Properties.

Pyridoxine (pyr) is a versatile molecule that forms part of the family of B vitamins. It is used to treat and prevent vitamin B6 deficiency and certain types of metabolic disorders. Moreover, the pyridoxine molecule has been investigated as a suitable ligand toward metal ions. Nevertheless, the study of the magnetic properties of metal complexes containing lanthanide(III) ions and this biomolecule is unexplored. We have synthesized and characterized a novel pyridoxine-based GdIII complex of formula [GdIII(pyr)2(H2O)4]Cl3 · 2 H2O (1) [pyr = pyridoxine]. 1 crystallizes in the triclinic system and space group Pi. In its crystal packing, cationic [Gd(pyr)2(H2O)4]3+ entities are connected through H-bonding interactions involving non-coordinating water molecules and chloride anions. In addition, Hirshfeld surfaces of 1 were calculated to further investigate their intermolecular interactions in the crystal lattice. Our investigation of the magnetic properties of 1, through ac magnetic susceptibility measurements, reveals the occurrence of a slow relaxation in magnetization in this mononuclear GdIII complex, indicating an unusual single-ion magnet (SIM) behavior for this pseudo-isotropic metal ion at very low temperatures. We also studied the relaxometric properties of 1, as a potential contrast agent for high-field magnetic resonance imaging (MRI), from solutions of 1 prepared in physiological serum (0.0-3.2 mM range) and measured at 3 T on a clinical MRI scanner. The values of relaxivity obtained for 1 are larger than those of some commercial MRI contrast agents based on mononuclear GdIII systems.

Magnetic-optical dual-modality imaging monitoring chemotherapy efficacy of pancreatic ductal adenocarcinoma with a low-dose fibronectin-targeting Gd-based contrast agent.

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is a lethal hypovascular tumor surrounded by dense fibrosis. Albumin-bound paclitaxel and gemcitabine (AG) chemotherapy is the mainstay of PDAC treatment through depleting peritumoral fibrosis and killing tumor cells; however, it remains challenging due to the lack of a noninvasive imaging method evaluating fibrotic changes during AG chemotherapy. In this study, we developed a dual-modality imaging platform that enables noninvasive, dynamic, and quantitative assessment of chemotherapy-induced fibrotic changes through near-infrared fluorescence molecular imaging (FMI) and magnetic resonance imaging (MRI) using an extradomain B fibronectin (EDB-FN)-targeted imaging probe (ZD2-Gd-DOTA-Cy7). METHODS: The ZD2-Gd-DOTA-Cy7 probe was constructed by conjugating a peptide (Cys-TVRTSAD) to Gd-DOTA and the near-infrared dye Cy7. PDAC murine xenograft models were intravenously injected with ZD2-Gd-DOTA-Cy7 at a Gd concentration of 0.05 mmol/kg or free Cy7 and Gd-DOTA as control. The normalized tumor background ratio (TBR) on FMI and the T1 reduction ratio on MRI were quantitatively analyzed. For models receiving AG chemotherapy or saline, MRI/FMI was performed before and after treatment. Histological analyses were performed for validation. RESULTS: The ZD2-Gd-DOTA-Cy7 concentration showed a linear correlation with the fluorescence intensity and T1 relaxation time in vitro. The optimal imaging time was 30 min after injection of the ZD2-Gd-DOTA-Cy7 (0.05 mmol/kg), only half of the clinic dosage of gadolinium. Additionally, ZD2-Gd-DOTA-Cy7 generated a 1.44-fold and 1.90-fold robust contrast enhancement compared with Cy7 (P < 0.05) and Gd-DOTA (P < 0.05), respectively. For AG chemotherapy monitoring, the T1 reduction ratio and normalized TBR in the fibrotic tumor areas were significantly increased by 1.99-fold (P < 0.05) and 1.78-fold (P < 0.05), respectively, in the control group compared with those in the AG group. CONCLUSION: MRI/FMI with a low dose of ZD2-Gd-DOTA-Cy7 enables sensitive imaging of PDAC and the quantitative assessment of fibrotic changes during AG chemotherapy, which shows potential clinical applications for precise diagnosis, post-treatment monitoring, and disease management.

Protease-Mediated T1 Contrast Enhancement of Multilayered Magneto-Gadolinium Nanostructures for Imaging and Magnetic Hyperthermia.

In this work, we constructed a multifunctional composite nanostructure for combined magnetic hyperthermia therapy and magnetic resonance imaging based on T1 and T2 signals. First, iron oxide nanocubes with a benchmark heating efficiency for magnetic hyperthermia were assembled within an amphiphilic polymer to form magnetic nanobeads. Next, poly(acrylic acid)-coated inorganic sodium gadolinium fluoride nanoparticles were electrostatically loaded onto the magnetic nanobead surface via a layer-by-layer approach by employing a positively charged enzymatic-cleavable biopolymer. The positive-negative multilayering process was validated through the changes occurring in surface ζ-potential values and structural characterization by transmission electron microscopy (TEM) imaging. These nanostructures exhibit an efficient heating profile, in terms of the specific absorption rates under clinically accepted magnetic field conditions. The addition of protease enzyme mediates the degradation of the surface layers of the nanostructures with the detachment of gadolinium nanoparticles from the magnetic beads and exposure to the aqueous environment. Such a process is associated with changes in the T1 relaxation time and contrast and a parallel decrease in the T2 signal. These structures are also nontoxic when tested on glioblastoma tumor cells up to a maximum gadolinium dose of 125 µg mL-1, which also corresponds to a iron dose of 52 µg mL-1. Nontoxic nanostructures with such enzyme-triggered release mechanisms and T1 signal enhancement are desirable for tracking tumor microenvironment release with remote T1-guidance and magnetic hyperthermia therapy actuation to be done at the diseased site upon verification of magnetic resonance imaging (MRI)-guided release.

NIR-Light-Triggered Mild-Temperature Hyperthermia to Overcome the Cascade Cisplatin Resistance for Improved Resistant Tumor Therapy.

Currently, cisplatin resistance has been recognized as a multistep cascade process for its clinical chemotherapy failure. Hitherto, it remains challenging to develop a feasible and promising strategy to overcome the cascade drug resistance (CDR) issue for achieving fundamentally improved chemotherapeutic efficacy. Herein, a novel self-assembled nanoagent is proposed, which is constructed by Pt(IV) prodrug, cyanine dye (cypate), and gadolinium ion (Gd3+), for systematically conquering the cisplatin resistance by employing near-infrared (NIR) light activated mild-temperature hyperthermia in tumor targets. The proposed nanoagents exhibit high photostability, GSH/H+-responsive dissociation, preferable photothermal conversion, and enhanced cellular uptake performance. In particular, upon 785-nm NIR light irradiation, the generated mild temperature of ≈ 43 °C overtly improves the cell membrane permeability and drug uptake, accelerates the disruption of intracellular redox balance, and apparently enhances the formation of Pt-DNA adducts, thereby effectively overcoming the CDR issue and achieves highly improved therapeutic efficacy for cisplatin-resistant tumor ablation.

Metabolomics-derived biomarkers for biosafety assessment of Gd-based nanoparticle magnetic resonance imaging contrast agents.

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.

α-Aryl substituted GdDOTA derivatives, the perfect contrast agents for MRI?

Enhancing the performance of Gd3+ chelates as relaxation agents for MRI has the potential to lower doses, improving safety and mitigating the environmental impact on our surface waters. More than three decades of research into manipulating the properties of Gd3+ have failed to develop a chelate that simultaneously optimizes all relevant parameters and affords maximal relaxivity. Introducing aryl substituents into the α-position of the pendant arms of a GdDOTA chelate affords chelates that, for the first time, simultaneously optimize all physico-chemical properties. Slowing tumbling by binding to human serum albumin affords a relaxivity of 110 ± 5 mM-1 s-1, close to the maximum possible. As discrete chelates, these α-aryl substituted GdDOTA chelates exhibit relaxivities that are 2-3 times higher than those of currently used agents, even at the higher fields (1.5 & 3.0 T) used in modern clinical MRI.