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1.
Biomed Mater ; 19(5)2024 Jul 03.
Article de Anglais | MEDLINE | ID: mdl-38870928

RÉSUMÉ

In this investigation, we embarked on the synthesis of polyethylene glycol coated NaGdF4:Tm3+/Yb3+upconversion nanoparticles (UCNPs), aiming to assess their utility in enhancing image contrast within the context of swept source optical coherence tomography (OCT) and photo-thermal OCT imaging. Our research unveiled the remarkable UC emissions stemming from the transitions of Tm3+ions, specifically the1G4→3H6transitions, yielding vibrant blue emissions at 472 nm. We delved further into the UC mechanism, meticulously scrutinizing decay times and the nanoparticles' capacity to convert radiation into heat. Notably, these nanoparticles exhibited an impressive photo-thermal conversion efficiency of 37.5%. Furthermore, our investigations into their bio-compatibility revealed a promising outcome, with more than 90% cell survival after 24 h of incubation with HeLa cells treated with UCNPs. The nanoparticles demonstrated a notable thermal sensitivity of 4.7 × 10-3K-1at 300 K, signifying their potential for precise temperature monitoring at the cellular level.


Sujet(s)
Survie cellulaire , Produits de contraste , Nanoparticules , Polyéthylène glycols , Tomographie par cohérence optique , Ytterbium , Tomographie par cohérence optique/méthodes , Humains , Cellules HeLa , Polyéthylène glycols/composition chimique , Ytterbium/composition chimique , Nanoparticules/composition chimique , Produits de contraste/composition chimique , Thermométrie/méthodes , Gadolinium/composition chimique , Thulium/composition chimique , Fluorures/composition chimique , Température , Matériaux revêtus, biocompatibles/composition chimique , Rayons infrarouges
2.
ACS Nano ; 18(24): 15416-15431, 2024 Jun 18.
Article de Anglais | MEDLINE | ID: mdl-38840269

RÉSUMÉ

The accumulation of amyloid-ß (Aß) peptides is a major hallmark of Alzheimer's disease (AD) and plays a crucial role in its pathogenesis. Particularly, the structured oligomeric species rich in ß-sheet formations were implicated in neuronal organelle damage. Addressing this formidable challenge requires identifying candidates capable of inhibiting peptide aggregation or disaggregating preformed oligomers for effective antiaggregation-based AD therapy. Here, we present a dual-functional nanoinhibitor meticulously designed to target the aggregation driving force and amyloid fibril spatial structure. Leveraging the exceptional structural stability and facile tailoring capability of endohedral metallofullerene Gd@C82, we introduce desired hydrogen-binding sites and charged groups, which are abundant on its surface for specific designs. Impressively, these designs endow the resultant functionalized-Gd@C82 nanoparticles (f-Gd@C82 NPs) with high capability of redirecting peptide self-assembly toward disordered, off-pathway species, obstructing the early growth of protofibrils, and disaggregating the preformed well-ordered protofibrils or even mature Aß fibrils. This results in considerable alleviation of Aß peptide-induced neuronal cytotoxicity, rescuing neuronal death and synaptic loss in primary neuron models. Notably, these modifications significantly improved the dispersibility of f-Gd@C82 NPs, thus substantially enhancing its bioavailability. Moreover, f-Gd@C82 NPs demonstrate excellent cytocompatibility with various cell lines and possess the ability to penetrate the blood-brain barrier in mice. Large-scale molecular dynamics simulations illuminate the inhibition and disaggregation mechanisms. Our design successfully overcomes the limitations of other nanocandidates, which often overly rely on hydrophobic interactions or photothermal conversion properties, and offers a viable direction for developing anti-AD agents through the inhibition and even reversal of Aß aggregation.


Sujet(s)
Maladie d'Alzheimer , Peptides bêta-amyloïdes , Neurones , Peptides bêta-amyloïdes/métabolisme , Peptides bêta-amyloïdes/antagonistes et inhibiteurs , Peptides bêta-amyloïdes/composition chimique , Maladie d'Alzheimer/traitement médicamenteux , Maladie d'Alzheimer/métabolisme , Maladie d'Alzheimer/anatomopathologie , Animaux , Neurones/effets des médicaments et des substances chimiques , Neurones/métabolisme , Neurones/anatomopathologie , Humains , Gadolinium/composition chimique , Gadolinium/pharmacologie , Nanoparticules/composition chimique , Fullerènes/composition chimique , Fullerènes/pharmacologie , Agrégats de protéines/effets des médicaments et des substances chimiques , Souris , Conception de médicament , Survie cellulaire/effets des médicaments et des substances chimiques , Rats
3.
Anal Chem ; 96(26): 10738-10747, 2024 Jul 02.
Article de Anglais | MEDLINE | ID: mdl-38898770

RÉSUMÉ

Herein, CsPbBr3 perovskite quantum dots (CPB PQDs)@poly(methyl methacrylate) (PMMA) (CPB@PMMA) nanospheres were used as energy donors with high Förster resonance energy transfer (FRET) efficiency and exceptional biocompatibility for ultrasensitive dynamic imaging of tiny amounts of microRNAs in living cells. Impressively, compared with traditional homogeneous single QDs as energy donors, CPB@PMMA obtained by encapsulating numerous CPB PQDs into PMMA as energy donors could not only significantly increase the efficiency of FRET via improving the local concentration of CPB PQDs but also distinctly avoid the problem of cytotoxicity caused by divulged heavy metal ions entering living cells. Most importantly, in the presence of target miRNA-21, DNA dendrimer-like nanostructures labeled with 6-carboxy-tetramethylrhodamine (TAMRA) were generated by the exposed tether interhybridization of the Y-shape structure, which could wrap around the surface of CPB@PMMA nanospheres to remarkably bridge the distance of FRET and increase the opportunity for effective energy transfer, resulting in excellent precision and accuracy for ultrasensitive and dynamic imaging of miRNAs. As proof of concept, the proposed strategy exhibited ultrahigh sensitivity with a detection limit of 45.3 aM and distinctly distinguished drug-irritative miRNA concentration abnormalities with living cells. Hence, the proposed enzyme-free CPB@PMMA biosensor provides convincing evidence for supplying accurate information, which could be expected to be a powerful tool for bioanalysis, diagnosis, and prognosis of human diseases.


Sujet(s)
Transfert d'énergie par résonance de fluorescence , microARN , Oxydes , Boîtes quantiques , Titane , Boîtes quantiques/composition chimique , microARN/analyse , Humains , Titane/composition chimique , Oxydes/composition chimique , Composés du calcium/composition chimique , Poly(méthacrylate de méthyle)/composition chimique , Plomb/composition chimique , Plomb/analyse , Gadolinium/composition chimique
4.
ACS Nano ; 18(26): 16516-16529, 2024 Jul 02.
Article de Anglais | MEDLINE | ID: mdl-38912600

RÉSUMÉ

Activated guided irradiation by X-ray (AGuIX) nanoparticles are gadolinium-based agents that have the dual benefit of mimicking the effects of a magnetic resonance imaging (MRI) contrast agent used in a clinical routine and enhancing the radiotherapeutic activity of conventional X-rays (for cancer treatment). This "theragnostic" action is explained on the one hand by the paramagnetic properties of gadolinium and on the other hand by the generation of high densities of secondary radiation following the interaction of ionizing radiation and high-Z atoms, which leads to enhanced radiation dose deposits within the tumors where the nanoparticles accumulate. Here, we report the results of a phase I trial that aimed to assess the safety and determine the optimal dose of AGuIX nanoparticles in combination with chemoradiation and brachytherapy in patients with locally advanced cervical cancer. AGuIX nanoparticles were administered intravenously and appropriately accumulated within tumors on a dose-dependent manner, as assessed by T1-weighted MRI, with a rapid urinary clearance of uncaught nanoparticles. We show that the observed tumor accumulation of the compounds can support precise delineation of functional target volumes at the time of brachytherapy based on gadolinium enhancement. AGuIX nanoparticles combined with chemoradiation appeared well tolerated among the 12 patients treated, with no dose-limiting toxicity observed. Treatment yielded excellent local control, with all patients achieving complete remission of the primary tumor. One patient had a distant tumor recurrence. These results demonstrate the clinical feasibility of using theranostic nanoparticles to augment the accuracy of MRI-based treatments while focally enhancing the radiation activity in tumors.


Sujet(s)
Gadolinium , Imagerie par résonance magnétique , Nanoparticules , Tumeurs du col de l'utérus , Gadolinium/composition chimique , Humains , Tumeurs du col de l'utérus/imagerie diagnostique , Tumeurs du col de l'utérus/traitement médicamenteux , Tumeurs du col de l'utérus/thérapie , Tumeurs du col de l'utérus/anatomopathologie , Femelle , Nanoparticules/composition chimique , Adulte d'âge moyen , Curiethérapie , Produits de contraste/composition chimique , Rayons X , Adulte , Sujet âgé , Chimioradiothérapie
5.
Acta Biomater ; 182: 199-212, 2024 07 01.
Article de Anglais | MEDLINE | ID: mdl-38734283

RÉSUMÉ

Reducing plaque lipid content and enhancing plaque stability without causing extensive apoptosis of foam cells are ideal requirements for developing a safe and effective treatment of atherosclerosis. In this study, we synthesized IR780-Gd-OPN nanomicelles by conjugating osteopontin (OPN) and loading a gadolinium-macrocyclic ligand (Gd-DOTA) onto near-infrared dye IR780-polyethylene glycol polymer. The nanomicelles were employed for mild phototherapy of atherosclerotic plaques and dual-mode imaging with near-infrared fluorescence and magnetic resonance. In vitro results reveal that the mild phototherapy mediated by IR780-Gd-OPN nanomicelles not only activates heat shock protein (HSP) 27 to protect foam cells against apoptosis but also inhibits the nuclear factor kappa-B (NF-κB) pathway to regulate lipid metabolism and macrophage polarization, thereby diminishing the inflammatory response. In vivo results further validate that mild phototherapy effectively reduces plaque lipid content and size while simultaneously enhancing plaque stability by regulating the ratio of M1 and M2-type macrophages. In summary, this study presents a promising approach for developing a safe and highly efficient method for the precise therapeutic visualization of atherosclerosis. STATEMENT OF SIGNIFICANCE: The rupture of unstable atherosclerotic plaques is a major cause of high mortality rates in cardiovascular diseases. Therefore, the ideal outcome of atherosclerosis treatment is to reduce plaque size while enhancing plaque stability. To address this challenge, we designed IR780-Gd-OPN nanomicelles for mild phototherapy of atherosclerosis. This treatment can effectively reduce plaque size while significantly improving plaque stability by increasing collagen fiber content and elevating the ratio of M2/M1 macrophages, which is mainly attributed to the inhibition of the NF-κB signaling pathway by mild phototherapy-activated HSP27. In summary, our proposed mild phototherapy strategy provides a promising approach for safe and effective treatment of atherosclerosis.


Sujet(s)
Micelles , Facteur de transcription NF-kappa B , Photothérapie , Plaque d'athérosclérose , Plaque d'athérosclérose/anatomopathologie , Animaux , Facteur de transcription NF-kappa B/métabolisme , Souris , Indoles/composition chimique , Indoles/pharmacologie , Mâle , Gadolinium/composition chimique , Gadolinium/pharmacologie , Cellules RAW 264.7 , Transduction du signal/effets des médicaments et des substances chimiques , Nanoparticules/composition chimique , Souris de lignée C57BL , Évolution de la maladie , Humains
6.
Phys Med ; 122: 103382, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38820805

RÉSUMÉ

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.


Sujet(s)
Tomodensitométrie , Iode , Rapport signal-bruit , Traitement d'image par ordinateur/méthodes , Gadolinium/composition chimique , Fantômes en imagerie
7.
ACS Appl Mater Interfaces ; 16(21): 27028-27039, 2024 May 29.
Article de Anglais | MEDLINE | ID: mdl-38755114

RÉSUMÉ

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.


Sujet(s)
Enrofloxacine , Colorants fluorescents , Enrofloxacine/analyse , Enrofloxacine/sang , Enrofloxacine/urine , Colorants fluorescents/composition chimique , Gadolinium/composition chimique , Nanostructures/composition chimique , Antibactériens/composition chimique , Antibactériens/analyse , Antibactériens/urine , Humains , Limite de détection , Spectrométrie de fluorescence , Naphtacènes/composition chimique
8.
J Nanobiotechnology ; 22(1): 289, 2024 May 27.
Article de Anglais | MEDLINE | ID: mdl-38802863

RÉSUMÉ

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.


Sujet(s)
Alginates , Produits de contraste , Gadolinium , Hydrogels , Imagerie par résonance magnétique , Microsphères , Imagerie par résonance magnétique/méthodes , Gadolinium/composition chimique , Animaux , Alginates/composition chimique , Hydrogels/composition chimique , Produits de contraste/composition chimique , Cicatrisation de plaie/effets des médicaments et des substances chimiques , Réactifs réticulants/composition chimique , Gélatine/composition chimique , Souris , Structures d'échafaudage tissulaires/composition chimique
9.
Nat Commun ; 15(1): 3902, 2024 May 09.
Article de Anglais | MEDLINE | ID: mdl-38724527

RÉSUMÉ

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.


Sujet(s)
Nanofils , Polymères , Nanofils/composition chimique , Animaux , Souris , Polymères/composition chimique , Lignée cellulaire tumorale , Gadolinium/composition chimique , Gadolinium/pharmacologie , Souris de lignée C57BL , Lymphocytes T CD8+/immunologie , Lymphocytes T CD8+/effets des médicaments et des substances chimiques , Vaccins anticancéreux/immunologie , Femelle , Humains , Vaccination/méthodes , Tumeurs/immunologie
10.
Anal Chem ; 96(19): 7697-7705, 2024 May 14.
Article de Anglais | MEDLINE | ID: mdl-38697043

RÉSUMÉ

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.


Sujet(s)
Lanthanides , Imagerie par résonance magnétique , Nanoparticules , Polymères , Semiconducteurs , Imagerie par résonance magnétique/méthodes , Animaux , Lanthanides/composition chimique , Polymères/composition chimique , Nanoparticules/composition chimique , Souris , Humains , Gadolinium/composition chimique , Luminescence , Oxygène singulet/composition chimique , Yttrium/composition chimique , Fluorures/composition chimique , Souris nude
11.
Chemosphere ; 357: 142090, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38648983

RÉSUMÉ

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.


Sujet(s)
Lanthane , Terres rares , Terres rares/composition chimique , Humains , Lanthane/composition chimique , Animaux , Cérium/composition chimique , Gadolinium/composition chimique , Structures macromoléculaires/composition chimique
12.
Molecules ; 29(8)2024 Apr 17.
Article de Anglais | MEDLINE | ID: mdl-38675647

RÉSUMÉ

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.


Sujet(s)
Produits de contraste , Nanoparticules magnétiques d'oxyde de fer , Imagerie par résonance magnétique , Nanoparticules de magnétite , Nanomédecine théranostique , Nanoparticules magnétiques d'oxyde de fer/composition chimique , Imagerie par résonance magnétique/méthodes , Produits de contraste/composition chimique , Nanoparticules de magnétite/composition chimique , Nanoparticules de magnétite/usage thérapeutique , Humains , Or/composition chimique , Dextrane/composition chimique , Gadolinium/composition chimique , Propriétés de surface , Hyperthermie provoquée/méthodes , Taille de particule
13.
Inorg Chem ; 63(18): 8462-8475, 2024 May 06.
Article de Anglais | MEDLINE | ID: mdl-38642052

RÉSUMÉ

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.


Sujet(s)
Composés azabicycliques , Chélateurs , Produits de contraste , Gadolinium , Imagerie par résonance magnétique , Produits de contraste/composition chimique , Animaux , Souris , Chélateurs/composition chimique , Chélateurs/synthèse chimique , Gadolinium/composition chimique , Complexes de coordination/composition chimique , Complexes de coordination/synthèse chimique , Structure moléculaire , Stéréoisomérie , Humains , Femelle
15.
J Control Release ; 369: 775-785, 2024 May.
Article de Anglais | MEDLINE | ID: mdl-38604386

RÉSUMÉ

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.


Sujet(s)
Encéphale , Préparations à action retardée , Propofol , Animaux , Propofol/pharmacocinétique , Propofol/administration et posologie , Propofol/sang , Propofol/composition chimique , Encéphale/métabolisme , Encéphale/imagerie diagnostique , Nanoparticules/administration et posologie , Mâle , Libération de médicament , Macaca mulatta , Vecteurs de médicaments/composition chimique , Imagerie par résonance magnétique , Barrière hémato-encéphalique/métabolisme , Systèmes de délivrance de médicaments , Gadolinium/administration et posologie , Gadolinium/composition chimique , Gadolinium/pharmacocinétique
16.
Radiol Phys Technol ; 17(2): 441-450, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38630390

RÉSUMÉ

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.


Sujet(s)
Produits de contraste , Hafnium , Nanoparticules , Oxydes , Fantômes en imagerie , Tomodensitométrie , Produits de contraste/composition chimique , Oxydes/composition chimique , Hafnium/composition chimique , Nanoparticules/composition chimique , Gadolinium/composition chimique , Iode/composition chimique , Rapport signal-bruit
17.
Chembiochem ; 25(10): e202400087, 2024 May 17.
Article de Anglais | MEDLINE | ID: mdl-38439618

RÉSUMÉ

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.


Sujet(s)
Aquaporine-1 , Gènes rapporteurs , Imagerie par résonance magnétique , Membre 1B3 de la famille des transporteurs d'anions organiques appartenant aux transporteurs de solutés , Eau , Eau/composition chimique , Humains , Imagerie par résonance magnétique/méthodes , Aquaporine-1/métabolisme , Aquaporine-1/génétique , Membre 1B3 de la famille des transporteurs d'anions organiques appartenant aux transporteurs de solutés/métabolisme , Membre 1B3 de la famille des transporteurs d'anions organiques appartenant aux transporteurs de solutés/génétique , Gadolinium/composition chimique , Produits de contraste/composition chimique , Produits de contraste/métabolisme , Cellules HEK293 , Animaux
18.
Chemistry ; 30(28): e202400344, 2024 May 17.
Article de Anglais | MEDLINE | ID: mdl-38469901

RÉSUMÉ

[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.


Sujet(s)
Produits de contraste , Complexes de coordination , Gadolinium , Composés organométalliques , Gadolinium/composition chimique , Cinétique , Produits de contraste/composition chimique , Complexes de coordination/composition chimique , Composés organométalliques/composition chimique , Ligands , Composés hétérocycliques/composition chimique , Imagerie par résonance magnétique , Humains
19.
Anal Sci ; 40(6): 1043-1050, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38430367

RÉSUMÉ

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.


Sujet(s)
Gadolinium , Imagerie par résonance magnétique , Cellules souches , Gadolinium/composition chimique , Animaux , Souris , Cellules souches/cytologie , Rayons infrarouges , Transplantation de cellules souches , Nanoparticules/composition chimique , Imagerie optique , Lanthanides/composition chimique , Tissu adipeux/cytologie
20.
Int J Mol Sci ; 25(4)2024 Feb 09.
Article de Anglais | MEDLINE | ID: mdl-38396789

RÉSUMÉ

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.


Sujet(s)
Gadolinium , Pyridoxine , Gadolinium/composition chimique , Aimants , Imagerie par résonance magnétique/méthodes , Ions
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