Contrast Reagent Research Articles

Putting biomonitors to work: native moss as a screening tool for solid waste incineration

Solid waste incineration (SWI) can release numerous air pollutants although the geographic reach of emissions is not routinely monitored. While many studies use moss and lichens for biomonitoring trace elements, including around SWIs, few investigate the complex, multi-element footprint expected from SWI emissions. This study develops using native moss as a screening tool for SWI while also informing community concerns about an aging incinerator in rural Oregon, USA. Trained community volunteers helped collect 36 composite samples of epiphytic moss (Orthotrichum s.l.) along a 32-km transect from the SWI. We used ICP-MS to measure 40 elements in moss, including 14 rare earth elements (REEs) previously unexplored for SWI. We compared the elemental signatures of samples with an emissions profile for SWI and modeled relationships between element concentrations and distance from the facility using nonparametric regression. The chemical signatures in moss pointed to SWI as a source, potentially through both stack and fugitive dust emissions. The strongest models described farther-dispersing elements, including mercury and cadmium (xR2 = 0.65 and 0.62, respectively), and suggested most deposition occurs within 5 to 10 km of the facility. Elements often associated with soil and dust, like arsenic and chromium, exhibited localized peaks within 0.2 km of the incinerator (xR2 = 0.14–0.3). Three novel elements—cesium and REEs europium and gadolinium—also showed promise as atmospheric tracers for SWI. Gadolinium, a contrast reagent for MRIs, could reflect medical waste incineration by the facility. We include additional analysis and discussion to help stakeholders use results effectively.

B-Glycine as a marker for β cell imaging and β cell mass evaluation.

β cell mass (BCM) and function are essential to the diagnosis and therapy of diabetes. Diabetic patients serve β cell loss is, and damage of β cells leads to severe insulin deficiency. Our understanding of the role of BCM in diabetes progression is extremely limited by lacking efficient methods to evaluate BCM in vivo. In vitro methods of labeling islets, including loading of contrast reagent or integration of exogenous biomarker, require artificial manipulation on islets, of which the clinical application is limited. Imaging methods targeting endogenous biomarkers may solve the above problems. However, traditional reagents targeting GLP-1R and VAMT2 result in a high background of adjacent tissues, complicating the identification of pancreatic signals. Here, we report a non-invasive and quantitative imaging technique by using radiolabeled glycine mimics ([18F]FBG, a boron-trifluoride derivative of glycine) to assay islet function and monitor BCM changes in living animals. Glycine derivatives, FBG, FBSa, 2Me-FBG, 3Me-FBG, were successfully synthesized and labeled with 18F. Specificity of glycine derivatives were characterized by in vitro experiment. PET imaging and biodistribution studies were performed in animal models carring GLYT over-expressed cells. In vivo evaluation of BCM with [18F]FBG were performed in STZ (streptozocin) induced T1D (type 1 diabetes) models. GLYT responds to excess blood glycine levels and transports glycine into islet cells to maintain the activity of the glycine receptor (GLYR). Best PET imaging condition was 80min after given a total of 240 ~ 250 nmol imaging reagent (a mixture of [18F]FBG and natural glycine) intravenously. [18F]FBG can detect both endogenous and exogenous islets clearly in vivo. When applied to STZ induced T1D mouse models, total uptake of [18F]FBG in the pancreas exhibited a linear correlation with survival BCM. [18F]FBG targeting the endogenous glycine transporter (GLYT), which is highly expressed on islet cells, avoiding extra modification on islet cells. Meanwhile the highly restricted expression pattern of GLYT excluded the background in adjacent tissues. This [18F]FBG-based imaging technique provides a non-invasive method to quantify BCM in vivo, implying a new evaluation index for diabetic assessment.

Implementation of The Paris System for Reporting Urine Cytology improves diagnostic accuracy of selective upper urinary tract cytology.

The Paris System for Reporting Urine Cytology (TPS) recommends diagnostic criteria for urinary tract cytology, focusing primarily on the detection of high-grade urothelial carcinoma (HGUC) in the lower urinary tract. The second edition of TPS (TPS 2.0), published in 2022, extends these recommendations to the upper urinary tract (UUT); however, there is a lack of comprehensive data on this subject. In total, 223 consecutive UUT cytology specimens from 137 patients were retrieved and reclassified according to TPS 2.0 criteria and were compared with the original diagnosis based on the conventional system (CS). Histologic follow-up within a 3-month period was conducted for 43 patients. Histologic follow-up revealed 30 HGUCs, five low-grade urothelial carcinomas (LGUCs), and eight nonneoplastic fibrotic tissues. The risk of high-grade malignancy for each TPS diagnostic category was 16.7% for nondiagnostic/unsatisfactory, 2.3% for negative for HGUC (NHGUC), 42.1% for atypical urothelial cells, 50.0% for suspicious for HGUC (SHGUC), and 81.8% for HGUC. In all five cases of histologically diagnosed LGUC, the cytologic diagnosis was NHGUC. When SHGUC/HGUC was considered positive, the diagnostic accuracy of TPS had 63% sensitivity, 95% specificity, a 90% negative predictive value, and a 79% positive predictive value, which were better than those of CS. In addition, the TPS indices did not differ significantly between the specimens obtained before and after the application of contrast reagents. TPS implementation improved the accuracy of UUT cytology in predicting histologic HGUC, which was unaffected by the application of contrast reagents. These data indicate the usefulness of TPS for UUT cytology in routine clinical settings.

One-Pot Three Carbon Dots with Various Lifetimes Rooted in Different Decarboxylation Degrees for Matrix-Free, Anti-Oxygen, and Time-Resolved Information Encryption and Cellular Imaging.

Activating long-lived room temperature phosphorescence (RTP) in the aqueous environment and thus realizing matrix-free, anti-oxygen, and time-resolved information encryption and cellular imaging remain a great challenge. Here, we fabricated three types of carbon dots (C-dots), i.e., fluorescent C-dots (F-C-dots) and two types of phosphorescent C-dots denoted as Pw-C-dots and Py-C-dots by a one-pot strategy. Their formation was attributed to the difference in the decarboxylation degree at high temperatures using trimesic acid (TMA) as a sole precursor. Unexpectedly, the yield reached as high as ∼92%, and the proportions were ∼27% for F-C-dots, ∼17% for Pw-C-dots, and ∼56% for Py-C-dots. These nanomaterials could help implement carbon peaking and carbon neutrality. Both green RTP of the two C-dots resulted from the small energy gap (ΔEST). These two RTP C-dots had a long lifetime of over 270 ms with a relatively high quantum yield (4.5 and 6.2%). They exhibited excellent photostability and anti-photobleaching performances. The dry and wet powders of the RTP C-dots were applied to high-level information encryption. The lifelike patterns were greatly different from those of the original ones and could last for several seconds to the naked eye, demonstrating that the RTP C-dots could be potentially employed as anti-oxygen and time-resolved contrast reagents. Most significantly, the cellular imaging experiments showed that the biofriendly PVP-coated Py-C-dots could localize at lysosomes and sustain hundreds of milliseconds. This approach not only pioneers a time-resolved lysosome localization model but also opens up a promising door for anti-oxygen and time-resolved RTP cytoimaging.

Multidrug resistance protein 1 silencing in osteosarcoma and chondrosarcoma cell lines.

The poor response of metastatic osteo- and chondrosarcomas to chemotherapy could be the result of multidrug resistance (MDR), which may be overcome through the use of small interfering RNA (siRNA). However, several methodologic questions remain unresolved. To test the toxicity of three commonly used siRNA transfection reagents and apply the least toxic reagent to investigate the siRNA-induced MDR1 mRNA knockdown. The toxicity of TransIT-TKO, Lipofectamine 2000, and X-tremeGENE siRNA transfection reagents was investigated on osteosarcoma (MG-63) and chondrosarcoma (SW1353) cell lines. The toxicity was measured at 4 and 24 hours using a MTT toxicity assay. The least toxic transfection reagent was applied to investigate the siRNA-induced MDR1 mRNA knockdown effect using qRT-PCR. Furthermore, five housekeeping genes were assessed in the BestKeeper software to obtain mRNA expression normalization. Lipofectamine 2000 was the least toxic transfection reagent, reducing the cell viability only in chondrosarcoma 24 hours following exposure to the highest dose. In contrast, TransIT-TKO and X-tremeGENE transfection reagents displayed a significant reduction in cell viability in both chondrosarcoma after 4 hours and in osteosarcoma after 24 hours. Significant MDR1 mRNA silencing of over 80% was achieved in osteo- and chondrosarcoma using Lipofectamine at a final siRNA concentration of 25 nM. No significant dose response was observed in knockdown efficiency in either Lipofectamine or siRNA concentration. Lipofectamine 2000 was the least toxic transfection reagent in osteo- and chondrosarcoma. Successful siRNA-induced MDR1 mRNA silencing of over 80% was achieved.

Design principles of bioinspired interfaces for biomedical applications in therapeutics and imaging.

In the past two decades, we have witnessed rapid developments in nanotechnology, especially in biomedical applications such as drug delivery, biosensing, and bioimaging. The most commonly used nanomaterials in biomedical applications are nanoparticles, which serve as carriers for various therapeutic and contrast reagents. Since nanomaterials are in direct contact with biological samples, biocompatibility is one of the most important issues for the fabrication and synthesis of nanomaterials for biomedical applications. To achieve specific recognition of biomolecules for targeted delivery and biomolecular sensing, it is common practice to engineer the surfaces of nanomaterials with recognition moieties. This mini-review summarizes different approaches for engineering the interfaces of nanomaterials to improve their biocompatibility and specific recognition properties. We also focus on design strategies that mimic biological systems such as cell membranes of red blood cells, leukocytes, platelets, cancer cells, and bacteria.

Discussion on Technical Evaluation Requirements of Allergen Detection Reagent Pre-marketing

In the perspective of technical evaluation, the pre-marketing regulatory requirements of allergen detection reagents in China, America, European Union were compared, and the regulatory risks and performance requirements of this product were analyzed based on the monitoring of post-marketing adverse events, reference standards and domestic and foreign regulatory documents. In view of the "neck-stuck" problems such as the difficulty of clinical trials, the difficulty of finding comparable contrast reagents and the lack of clinical diagnostic gold standards, this paper discusses and gives regulatory suggestions, with a view to providing technical reference for product R&D, production, evaluation, approval and supervision in this field.

Electron-deficient N-oxyl radicals – new reagents for selective oxidative functionalization of organic substrates

N-oxyl radicals are well known as one of the richest classes of long-living free radicals. They are widely used as redox catalysts, mediators of living polymerization, contrast reagents for tomography applications, spin labels for biomacromolecule studies, components of organic batteries and magnetic materials. In the last decade, less stable but more reactive electron-deficient N-oxyl radicals have been harnessed as reagents for oxidative functionalization of organic substrates via selective C-H bond cleavage or radical addition to C = C bonds. Wide array of C-O coupling products can be achieved employing N-oxyl radicals as O-reagents for oxidative C-O coupling. Selected examples of methods for oxidative functionalization of organic substrates by N-oxyl radicals developed in our group are summarized in the present paper.

Rare Earth Elements and Yttrium (REE+Y) patterns in recent Anadara brasiliana shells from Playa Norte, Barra de Cazones (Veracruz, Mexico): Evidence of anthropogenic contamination linked to river output?

We measured and interpreted Rare Earth Element and Yttrium concentrations of ten recent Anadara brasiliana (Lamarck) shells from Playa Norte (Barra de Cazones, Veracruz, Mexico). We aimed to identify the source of these elements, along with addressing some environmental conditions attributable to them. REE + Y patterns show modern seawater signals, particularly positive La/La* and Y/Y* anomalies as well as marked depletions of light REEs and middle REEs in comparison to heavy REEs) (x̄ PrSN/YbSN = 0.127, x̄ NdSN/YbSN = 0.16 and x̄ DySN/YbSN = 0.444, respectively). The cause for La/La* anomalies can also be explained by means of anthropogenic contamination, yet this question remains unresolved. Pronounced negative cerium anomalies were also recognised [(Ce/Ce*) = 0.262], which point to oxidising conditions. Y/Ho ratios (ranging from 35.85 to 64.91; average = 44.68) are in part superchondritic (range 44–74). Values lower than these (35.85–39.83) may account for the closeness to the nearby-flowing Cazones River, which runs through many important cities and populations in Veracruz, such as Poza Rica, Coatzintla and Barra de Cazones.In addition to the referred REE anomalies, we report notable positive Sm/Sm* and Gd/Gd* anomalies. The former may be an evidence of contamination caused by petroleum industry in this region, which is well known for its hydrocarbon production. For its part, the latter may mirror river contamination by means of contrast reagents poured into freshwater and ultimately into the ocean.This study shows the first results of a long-term project, which aims to elucidate the REE + Y dynamics in the Gulf of Mexico coastal system at the state of Veracruz, eastern Mexico.

A novel fuzzy blend scheme for image enhancement of CT scans bearing liver cancer

ABSTRACT This paper deals with the design of an image enhancement algorithm which is capable of improving the quality of computed tomography (CT) images for liver cancer diagnosis. A novel soft computing technique namely fuzzy blend scheme (FBS) is proposed in this work. The FBS works in two stages. The first stage is the pre-processing stage in which the image is de-noised and sharpened by the application of a non-linear filter. In the second stage, the pre-processed output is blended with a novel fuzzy transformation function to give the contrast-enhanced image. The method is tested on 181 CT images from 15 patients of liver cancer named hepatocellular carcinoma. Quality metrics computed for the comparison of FBS with the existing methods include signal to noise ratio = 11.4270, enhancement measure = 12.30, structural similarity index = 91% and discrete entropy which is less than original image. The maximum computation time for FBS is 3.488 s. The proposed method can aid the radiologists and physicians in disease diagnosis. It will help in reducing the burden of ionic contrast reagents induced in patients for tumour visualisation.

A novel method for π-shaped esophagojejunostomy and double-tract reconstruction (DTR) as an alternative in totally laparoscopic or robotic proximal gastrectomy for treating upper third proximal early gastric cancer.

This study evaluated the impact of a new intracorporeal π-shaped esophagojejunostomy (EJS) and double-tract reconstruction (DTR) in totally laparoscopic and totally robotic proximal gastrectomy (TLPG or TRPG) for treating upper third early gastric cancer (U-EGC) in terms of intraoperative and short-term postoperative outcomes. Early proximal gastric cancer patients were identified based on a prospectively established database. From January 2017 to December 2018, these patients underwent intracorporeal π-shaped EJS and DTR after totally laparoscopic (n = 8) or robotic (n = 4) proximal gastrectomy (PG). We recorded and analyzed the baseline characteristics and surgical outcomes, including postoperative complications for these patients. No severe postoperative complications were observed following the operational procedures. Twelve patients (seven male and five female) diagnosed with cardia cancer (Siewert II and III) were enrolled, of which eight underwent the totally laparoscopic proximal gastrectomy (TLPG), and four underwent the totally robotic proximal gastrectomy (TRPG). The mean operative time, blood loss, day of the start of the diet, and postoperative hospital stay was 235.54 ± 20.79min, 50.65 ± 35.44mL, 3.85 ± 0.65days, and 12.45 ± 3.24days, respectively. All patients presented with a diagnosis of stage I gastric cancer. The mean number of lymph node dissections and the maximum tumor diameter was 13.91 ± 4.63 and 2.18 ± 0.73cm, respectively. After the operational procedure, using the iodoethylene contrast reagent, we observed that a large proportion of iodoethylene contrast agents entered the jejunum directly, and a small proportion entered the jejunum through the duodenum. Surgeons followed up with ten patients for more than 12months and the remaining two patients for more than 24months. None of the patients showed any signs of anastomotic stenosis or reflux esophagitis or anemia symptoms. This study presents a novel method for π-shaped EJS and DTR as an alternative in TLPG or TRPG for treating proximal early gastric cancer, and it offers better short-term postoperative and intraoperative surgical outcomes.

Fabrication of gold nanohybrids modified with antibody and functional dendrimers for targeted photothermal theranostics

AbstractTargeted theranostics can improve benefits of therapeutics or imaging probes by minimizing the dose and by selective delivery to a target site. For this study, a gold nanorod (AuNR)‐based nanohybrid was designed for efficient cancer treatment and diagnosis. The AuNR was functionalized with polyamidoamine dendrimers having poly(ethylene glycol) and Gd‐DOTA residues to provide biocompatibility and magnetic resonance (MR) imaging properties. Furthermore, trastuzumab was conjugated to the obtained nanohybrids to enhance the delivery performance to HER2‐expressing tumor cells. Fabricated nanohybrids possessed uniform hydrodynamic diameter and showed typical surface plasmon absorption, which is useful to convert light energy to heat for photothermal therapy. Nanohybrids exhibited T1‐weighted relaxation and comparable MR imaging property to that of commercially available MR contrast reagent. In vitro experiments demonstrated that photothermal effects of nanohybrid under near infrared (NIR) irradiation were sufficient to kill 80%–90% of cancer cells. The combination of the targeted nanohybrid and NIR laser irradiation strongly suppressed tumor growth and extended the survival of HER2‐positive SKOV3 tumor‐bearing nude mice. Therefore, fabricated nanohybrids are promising for targeted photothermal therapy and imaging.

Dynamic Imaging of Mouse Embryos and Cardiac Development in Static Culture.

Dynamic imaging is a powerful approach to assess the function of a developing organ system. The heart is a dynamic organ that undergoes quickmorphological and mechanical changes through early embryonic development. Defining the embyonic mouseheart'snormal function is important for our ownunderstanding of human heartdevelopment and will inform us on treatments and prevention of congenital heart defects (CHD). Traditional methods such as ultrasound or fluorescence-based microscopy are suitablefor live dynamic imaging, are excellent to visualize structure and connect gene expression to phenotypes, but can be of low quality in resolving fine features and lack imaging depth and scale to fully appreciate organ morphogenesis. Additionally, previous methods can be limited in accommodating a live imaging apparatus capable of sustaining whole embryo development for extended periods time. Optical coherence tomography (OCT) is unique in this circumstance because acquisition of three-dimensional images without contrast reagents, at single cell resolution make it a suitablemodality to visualize fine structures in the developing embryo. OCT setups are highly customizable for live imaging because of the tethered imaging arm, due to its setup as a fiber-based interferometer. OCT allows for 4D (3D+time) functional imaging of living mouse embryos and can provide functional and mechanical information to ascertain how the heart's pump function changes through development. In this chapter, we will focus on how we use OCT to visualize live heart dynamics at different stages of development and provide mechanical information to reveal functional properties of the developing heart.

Two-photon imaging of aptamer-functionalized Copolymer/TPdye fluorescent organic dots targeted to cancer cells

Fluorescent organic dots (O-dots) recently have emerged as a new class of promising contrast reagents for two-photon fluorescence (TPF) imaging. However, most of these developed two-photon absorption (TPA) O-dots have no tumor-targeting group, which hampers their wide application for targeted tumor imaging. Herein, we fabricated Sgc8c aptamer-mediated TPA O-dots as a proof-of-concept of the sensing platform for targeted imaging in live cells or deep tissues. The O-dots composed of trans-4-[p-(N, N-diethylamino)styryl]-4’-(dimethyl amino) stilbene (DEAS) emerged as TPA organic emissive cores and encapsulation by using poly (methyl methacrylate-co-methacrylic acid) (PMMA-co-MAA) as polymeric encapsulating matrix to form DEAS/PMMA-co-MAA O-dots via a co-precipitation strategy. The obtained O-dots enabled an extremely high TPA absorption cross-section, bright two-photon fluorescence (excitation at 720 nm; emission at 412 nm and 434 nm), excellent cell-permeability and high penetration depth. Sgc8c aptamer, as a protein tyrosine kinase-7 (PTK7) receptor-targetable ligand, was further anchored on the surface of O-dots to obtain DEAS/PMMA-co-MAA@Sgc8c nanoprobes by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC)-mediated coupling reaction. Guided by Sgc8c aptamer, DEAS/PMMA-co-MAA@Sgc8c nanoprobes could be rapidly internalized into target acute lymphoblastic leukemia cells (CEM) cells with high specificity and great efficiency. It was also performed that two-photon images of TPA nanoprobes exhibited high two-photon brightness not only in target CEM cells, but also in mouse liver tissue slices even a depth of up to 210 μm. In our perception, it is highly promising that this nanoprobe provides a valuable tool for in vivo targeted imaging.

Visualization of internal 3D structure of small live seed on germination by laboratory-based X-ray microscopy with phase contrast computed tomography

BackgroundThe visualization of internal 3D-structure of tissues at micron resolutions without staining by contrast reagents is desirable in plant researches, and it can be achieved by an X-ray computed tomography (CT) with a phase-retrieval technique. Recently, a laboratory-based X-ray microscope adopting the phase contrast CT was developed as a powerful tool for the observation of weakly absorbing biological samples. Here we report the observation of unstained pansy seeds using the laboratory-based X-ray phase-contrast CT.ResultsA live pansy seed within 2 mm in size was simply mounted inside a plastic tube and irradiated by in-house X-rays to collect projection images using a laboratory-based X-ray microscope. The phase-retrieval technique was applied to enhance contrasts in the projection images. In addition to a dry seed, wet seeds on germination with the poorer contrasts were tried. The phase-retrieved tomograms from both the dry and the wet seeds revealed a cellular level of spatial resolutions that were enough to resolve cells in the seeds, and provided enough contrasts to delineate the boundary of embryos manually. The manual segmentation allowed a 3D rendering of embryos at three different stages in the germination, which visualized an overall morphological change of the embryo upon germination as well as a spatial arrangement of cells inside the embryo.ConclusionsOur results confirmed an availability of the laboratory-based X-ray phase-contrast CT for a 3D-structural study on the development of small seeds. The present method may provide a unique way to observe live plant tissues at micron resolutions without structural perturbations due to the sample preparation.

Mitochondriotropic lanthanide nanorods: implications for multimodal imaging.

Two-photon active mitochondriotropic lanthanide nanorods for high resolution fluorescence imaging. The presence of Gd in the nanorods also enabled us to utilize this material as a T1-T2 dual-mode contrast reagent for recording magnetic resonance images of the mouse brain.

Rat mandibular condyle and fossa grew separately then unified as a single joint at 20 days old, which was the weaning age.

Magnetic resonance imaging (MRI) was used to observe growth of the mandibular condyle, mandibular fossa, and articular disc as a single unit. Changes in each component's relative position and size were observed using 7-tesla MRI. Mandibular condyle chondrocytes' growth was evaluated with immunohistochemistry, using the expression of zinc transporter ZIP13. Three-dimensional T1-weighted (T1w) MRI was used to obtain images of the TMJ of Sprague Dawley rats at 4-78 days old (P4-78) with a voxel resolution of 65 μm. Two-dimensional T1w MR images were acquired after a subcutaneous injection of the contrast reagent gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA). The T1w MR images showed that the mandibular condyle was located posterior to the mandibular fossa until P20; however, it then moved to a location underneath the mandibular fossa. In the Gd-DTPA enhanced images, the articular disc was identified as a region with lower signal intensity from P20. The number of ZIP13-positive chondrocytes at P6 was larger than the number at P24. In conclusion, the mandibular condyle with cartilage and disc grows on the posterior side of the mandibular fossa until P20, which was the weaning age. Then, the condyle fit into the mandibular fossa and completed the functional unit.

Redox‐responsive polyethyleneimine‐coated magnetic iron oxide nanoparticles for controllable gene delivery and magnetic resonance imaging

AbstractRecently, theranostic candidates that provide a combination of gene delivery and image diagnosis have attracted much interest in medical research. However, there are still many challenges for their clinical applications, such as uncontrollable gene delivery, high cytotoxicity, low transfection efficiency and reduced image contrast. Herein, redox‐responsive polyethyleneimine‐coated magnetic iron oxide nanoparticles (IONs@rPEI) were prepared for both efficient gene delivery and magnetic resonance (MR) imaging. Firstly, crosslinked rPEI was synthesized by Michael addition reaction with N,N‐bis(acryloyl)cystamine, dopamine and low‐molecular‐weight branched PEI. The rPEI was then coated onto IONs by ligand exchange reaction forming IONs@rPEI. The physicochemical properties of the IONs@rPEI, such as chemical structure, size, zeta potential and DNA condensation ability, were investigated. In addition, a rapid degradation of the as‐prepared nanoparticles was observed, which was triggered by reducing glutathione via destruction of disulfide linkages suggesting a potential controllable DNA release in tumor cells. In MR imaging detection, the IONs@rPEI had a high T2 relaxivity of 81 L mmol−1 s−1 indicating a potential usage as MR imaging contrast reagent. In cell assay, the IONs@rPEI exhibited low cytotoxicity and good transfection efficiency. In conclusion, the as‐prepared crosslinked IONs@rPEI can be used as a promising technology platform for gene therapy and MR imaging in theranostics. © 2019 Society of Chemical Industry

Intra-articular tracking of adipose-derived stem cells by chitosan-conjugated iron oxide nanoparticles in a rat osteoarthritis model.

Adipose-derived stem cells (ADSCs) hold great potential in cartilage tissue engineering due to their multipotency and ease of availability. MRI is an effective and noninvasive imaging approach to track cells and observe new tissue regeneration. It is essential to find a compatible and efficient imaging reagent without affecting the stemness of ADSCs. Herein, we developed chitosan-modified iron oxide nanoparticles (IO-CS) as the T2 contrast reagent with good cell compatibility and high cellular uptake efficiency and used IO-CS for ADSC intra-articular imaging in a rat osteoarthritis (OA) model. TEM demonstrated the great morphology and size distribution of IO-CS nanoparticles with the size of 17 nm. Magnetization (29.4 emu per g) and MRI tests confirmed (R2 of 184 mM−1 s−1) the feasibility of IO-CS nanoparticles as an MRI contrast reagent. In addition, the IO-CS nanoparticles showed good cellular compatibility and high labeling efficiency as compared to the commercial agent ferumoxytol. Moreover, incorporation of IO-CS nanoparticles did not alter the adipogenic, osteogenic and chondrogenic differentiation ability of ADSCs. Furthermore, the MRI transverse R2 maps showed a persistence time of the IO-CS nanoparticles in ADSCs of 6 days in vitro. Then, we investigated the imaging capability of the IO-CS nanoparticle-labeled ADSCs in vivo with MRI for 5 weeks. The histological studies demonstrated the intra-articular biodistribution of the IO-CS nanoparticles, including in the cartilage superficial layer, synovial sublining layer, periosteum and bone marrow cavity. They provided systemic distribution information of the ADSCs in the OA rat model. In summary, we developed an accessible and effective T2 imaging reagent with good biocompatibility and maintenance of the stemness of ADSCs. This showed the potential translational application of IO-CS nanoparticles as an MRI reagent in cartilage tissue engineering.

In English

During last decades сoordination compounds of lanthanides with polychelating β-diketones and their derivatives have attracted increasing interest due to the possibility of using such compounds in biomedical research, as contrast reagents for NMR tomography studies and MOLED technology. That is why the selection of appropriate ligands, which are effective sensitizers of lanthanide luminescence and can form thermodynamically stable complexes, is especially important. Carbacylamidophosphates (CAPh ligands) of general formula (R 1 )C(O)NHP(O)(R 2 ) 2 are structural analogues of β-diketones, which can serve as an antenna providing more efficient energy transfer to the lanthanide ion followed by Ln(III) luminescence. The present work is devoted to the mass-spectrometric studies of the stability of coordination compound of terbium(III) with new CAPh ligand using methods of soft ionization such as matrix activated laser desorption / ionization (MALDI), its modification – LDI (laser desorption ionization). The main preference of the «soft ionization» methods is the possibility of unfragmented ions registration. Terbium coordination compound with new bis-chelating carbacylamidophosphate ligand (Tb(HL) 2 (NO 3 )) (where HL – = tetramethyl[pyridine-2,6-diyldi(iminocarbonyl)]diamidophosphate anion) has been synthesized and studied by IR spectroscopy and X-ray diffraction. It was shown that the deprotonated arm of each ligand is coordinated to the terbiumion in the bidentate manner and the protonated arm in monodentate manner via the oxygen atom of phosphoryl group. The nitrate ion is bidentate coordinated, completing coordination number of terbium to eight. The components of the LDI mass spectrum of the synthesized coordination compound have been identified. The positive region of the mass spectrum of the complex Tb(HL) 2 (NO 3 ) is characterized by the presence of smaller fragments due to the effect of the metal ion on the fragmentation of the ligand molecules and the molecular ion is not observed due to formation of more complex and stable structures based on Tb(III) ions.