Selective Uptake Research Articles

Hexacoordinated Sn(IV) porphyrin‐based square‐grid frameworks exhibiting selective uptake of CO2 over N2

AbstractWe prepared porphyrin metal–organic frameworks with hexacoordinated Sn(IV) porphyrin trans‐SnX2(TPyP), where X = Cl−, OH−; TPyP = 5,10,15,20‐tetra(4‐pyridyl)porphyrinato dianion, and Cu(II) acetate, namely {[SnCl2(TPyP)]⋅[Cu(OAc)2]4}⋅4DMF⋅4H2O (1) and {[Sn(OH)2(TPyP)]⋅[Cu(OAc)2]4}⋅xSolv (2). X‐ray crystallographic analysis revealed that both materials consisted of the same square‐grid two‐dimensional (2D) sheet. The small difference in the trans‐axial ligand coordinated to the Sn(IV) center creates distinctively different packing structures. As a consequence of the Cl⋯π and Cl⋯Cl interactions between the adjacent layers in 1, squares of stacked 2D layers are well aligned, giving a single type of ordered porous channel. In contrast, adjacent 2D layers in 2 are stacked along the c‐axis with an ABAB sequence with an average delamination of 7.05 Å. The coordination network structures of both materials provide large free voids without interpenetration. Gas sorption studies showed that both porous materials exhibit 10 times higher CO2 adsorption than N2 at 273 K.

Differential Clearance of Aβ Species from the Brain by Brain Lymphatic Endothelial Cells in Zebrafish.

The failure of amyloid beta (Aβ) clearance is a major cause of Alzheimer’s disease, and the brain lymphatic systems play a crucial role in clearing toxic proteins. Recently, brain lymphatic endothelial cells (BLECs), a non-lumenized lymphatic cell in the vertebrate brain, was identified, but Aβ clearance via this novel cell is not fully understood. We established an in vivo zebrafish model using fluorescently labeled Aβ42 to investigate the role of BLECs in Aβ clearance. We discovered the efficient clearance of monomeric Aβ42 (mAβ42) compared to oligomeric Aβ42 (oAβ42), which was illustrated by the selective uptake of mAβ42 by BLECs and peripheral transport. The genetic depletion, pharmacological inhibition via the blocking of the mannose receptor, or the laser ablation of BLECs resulted in the defective clearance of mAβ42. The treatment with an Aβ disaggregating agent facilitated the internalization of oAβ42 into BLECs and improved the peripheral transport. Our findings reveal a new role of BLECs in the differential clearance of mAβ42 from the brain and provide a novel therapeutic strategy based on promoting Aβ clearance.

Stabilized nanotube and nanofiber gel materials toward multifunctional adsorption

Incorporation of multiple functional molecules with unique structures can endow gel materials with outstanding performance in adsorption. Herein, self-assembly of structurally simple trispyridine molecules of 1,3,5-tris(4-pyridylmethoxyl)benzene achieves supramolecular gels with two different nanofiber or nanotube morphologies depending on difference in gelation temperature and cooling rate, and the self-assembled materials have been successfully stabilized though covalent capture to obtain stable nanofiber and nanotube materials with additional pillar[5]arene groups. Owing to the positively charged pyridinium networks, host-guest interaction of pillar[5]arene and different morphologies, the materials show diverse multifunctional adsorption performance, including selective uptake for cationic dye, molecular shape recognition for dinitrobenzene isomers, and remarkable adsorption for iodine capture. The tubular material shows boosted iodine adsorption via synergistic effect, and the capacity for iodine reaches up to 2.29 g g−1 via vapor adsorption and 2.95 g g−1 in solution.

Rapid and Selective Uptake of Cs+ and Sr2+ Ions by a Layered Thiostannate with Acid–Base and Irradiation Resistances

137Cs+ and 90Sr2+ are highly soluble, highly environmentally mobile, and strongly radiotoxic. Efficiently sequestering 137Cs+ and 90Sr2+ ions from aqueous solutions remains a serious challenge, esp...

PET Imaging of VLA-4 in a New BRAFV600E Mouse Model of Melanoma.

Despite unprecedented responses to immune checkpoint inhibitors and targeted therapy in melanoma, a major subset of patients progresses and have few effective salvage options. We have previously demonstrated robust, selective uptake of the peptidomimetic LLP2A labeled with Cu-64 ([64Cu]-LLP2A) for positron emission tomography (PET) imaging in subcutaneous and metastatic models of B16F10 murine melanoma. LLP2A binds with high affinity to very late antigen-4 (VLA-4, integrin α4β1), a transmembrane protein overexpressed in melanoma and other cancers that facilitates tumor growth and metastasis. Yet B16F10 fails to faithfully reflect human melanoma biology, as it lacks certain oncogenic driver mutations, including BRAF mutations found in ≥ 50 % of clinical specimens. Here, we evaluated the PET tracer [64Cu]-CB-TE1A1P-PEG4-LLP2A ([64Cu]-LLP2A) in novel, translational BRAFV600E mutant melanoma models differing in VLA-4 expression-BPR (VLA-4-) and BPRα (VLA-4+). BPR cells were transduced with α4 (CD49d) to overexpress intact cell surface VLA-4 (BPRα). The binding affinity of [64Cu]-LLP2A to BPR and BPRα cells was determined by saturation binding assays. [64Cu]-LLP2A internalization into B16F10, BPR, and BPRα cells was quantified via a plate-based assay. Tracer biodistribution and PET/CT imaging were evaluated in mice bearing subcutaneous BPR and BPRα tumors. [64Cu]-LLP2A demonstrated high binding affinity to BPRα (Kd = 1.4nM) but indeterminate binding to BPR cells. VLA-4+ BPRα and B16F10 displayed comparable time-dependent [64Cu]-LLP2A internalization, whereas BPR internalization was undetectable. PET/CT showed increased tracer uptake in BPRα tumors vs. BPR tumors in vivo, which was validated by significantly greater (p < 0.0001) BPRα tumor uptake in biodistribution analyses. [64Cu]-LLP2A discriminates BPRα (VLA-4+) vs. BPR (VLA-4-) melanomas in vivo, supporting translation of these BRAF-mutated melanoma models via prospective imaging and theranostic studies. These results extend the utility of LLP2A to selectively target clinically relevant and therapy-resistant tumor variants toward its use for therapeutic patient care.

Genome and Methylome analysis of a phylogenetic novel Campylobacter coli cluster with C. jejuni introgression.

The intriguing recent discovery of Campylobacter coli strains, especially of clade 1, that (i) possess mosaic C. coli / C. jejuni alleles, (ii) demonstrate mixed multilocus sequence types (MLSTs) and (iii) have undergone genome-wide introgression has led to the speculation that these two species may be involved in an accelerated rate of horizontal gene transfer that is progressively leading to the merging of both species in a process coined ‘despeciation’. In an MLST-based neighbour-joining tree of a number of C. coli and C. jejuni isolates of different clades, three prominent Campylobacter isolates formed a seemingly separate cluster besides the previously described C. coli and C. jejuni clades. In the light of the suspected, ongoing genetic introgression between the C. coli and C. jejuni species, this cluster of Campylobacter isolates is proposed to present one of the hybrid clonal complexes in the despeciation process of the genus. Specific DNA methylation as well as restriction modification systems are known to be involved in selective uptake of external DNA and their role in such genetic introgression remains to be further investigated. In this study, the phylogeny and DNA methylation of these putative C. coli / C. jejuni hybrid strains were explored, their genomic mosaic structure caused by C. jejuni introgression was demonstrated and basic phenotypic assays were used to characterize these isolates. The genomes of the three hybrid Campylobacter strains were sequenced using PacBio SMRT sequencing, followed by methylome analysis by Restriction-Modification Finder and genome analysis by Parsnp, Smash++ and blast. Additionally, the strains were phenotypically characterized with respect to growth behaviour, motility, eukaryotic cell invasion and adhesion, autoagglutination, biofilm formation, and water survival ability. Our analyses show that the three hybrid Campylobacter strains are clade 1 C . coli strains, which have acquired between 8.1 and 9.1 % of their genome from C. jejuni . The C. jejuni genomic segments acquired are distributed over the entire genome and do not form a coherent cluster. Most of the genes originating from C. jejuni are involved in chemotaxis and motility, membrane transport, cell signalling, or the resistance to toxic compounds such as bile acids. Interspecies gene transfer from C. jejuni has contributed 8.1–9.1% to the genome of three C. coli isolates and initiated the despeciation between C. jejuni and C. coli . Based on their functional annotation, the genes originating from C. jejuni enable the adaptation of the three strains to an intra-intestinal habitat. The transfer of a fused type II restriction-modification system that recognizes the CAYNNNNNCTC/GAGNNNNNRTG motif seems to be the key for the recombination of the C. jejuni genetic material with C. coli genomes.

Polyethylene oxide-polyacrylic acid-folic acid (PEO-PAAc) nanogel as a 99m Tc targeting receptor for cancer diagnostic imaging.

Nanoparticles are frequently used as targeting delivery systems for therapeutic and diagnostic radiopharmaceuticals. Polyethylene oxide-polyacrylic acid (PEO-PAAc) nanogel was prepared via γ-radiation-induced polymerization. Variable factors affecting nanoparticles size were investigated. The nanogel was radiolabeled with the imaging radioisotope 99m Tc and finally conjugated with folic acid to target folate receptor actively. PEO-PAAc-folic acid gel was characterized by dynamic light scattering (DLS) and atomic force microscopy (AFM). Biodistribution was studied in normal mice and solid tumor-bearing mice via intravenous and intratumor injections of the radiolabeled PEO-PAAc-folic acid nanogel. Results of biodistribution showed high selective uptake of the prepared complex in tumor muscle compared with normal muscle for both intravenous and intratumor injections. The T/NT ratio was found to be 6.186 and 294.5 for intravenous and intratumor injections, respectively. Consequently, 99m Tc-PEO-PAAc-folic acid complex could be a promising agent for cancer diagnostic imaging.

Aptamer-conjugated mesoporous polydopamine for docetaxel targeted delivery and synergistic photothermal therapy of prostate cancer.

ObjectivesIt is imperative to develop efficient strategies on the treatment of prostate cancer. Here, we constructed multifunctional nanoparticles, namely AS1411@MPDA‐DTX (AMD) for targeted and synergistic chemotherapy/photothermal therapy of prostate cancer.Materials and MethodsMesoporous polydopamine (MPDA) nanoparticles were prepared by a one‐pot synthesis method, DTX was loaded through incubation, and AS1411 aptamer was modified onto MPDA by the covalent reaction. The prepared nanoparticles were characterized by ultra‐micro spectrophotometer, Fourier transform infrared spectra, transmission electron microscope, and so on. The targeting ability was detected by selective uptake and cell killing. The mechanism of AMD‐mediated synergistic therapy was detected by Western blot and immunofluorescence.ResultsThe prepared nanoparticles can be easily synthesized and possessed excellent water solubility, stability, and controlled drug release ability, preferentially in acidic context. Based on in vitro and in vivo results, the nanoparticles can efficiently target prostate cancer cells, promote DTX internalization, and enhance the antitumor effects of chemo‐photothermal therapy strategies under the NIR laser irradiation.ConclusionsAs a multifunctional nanoplatform, AS1411@MPDA‐DTX could efficiently target prostate cancer cells, promote DTX internalization, and synergistically enhance the antiprostate cancer efficiency by combining with NIR irradiation.

Targeted delivery of doxorubicin through CD44 aptamer to cancer cells.

Aim: The current investigation is focused on the targeted delivery of doxorubicin through CD44 aptamer-mediated active targeting to the human breast cancer cells. Methods: CD44 aptamer-doxorubicin (Apt-Dox) conjugates were developed by incubating different molar ratios of aptamer and doxorubicin. Cytotoxicity, selective intracellular accumulation and uptake of the Apt-Dox conjugates were analyzed to evaluate the efficacy of Apt-Dox conjugates. Results: Dox was efficiently conjugated with aptamer at 1:2 Apt-Dox molar ratios. Apt-Dox conjugate significantly inhibited the proliferation of CD44-overexpressing breast cancer cells, whereas negligible inhibition of cell proliferation was found in the control cells. Apt-Dox conjugate selectively internalized andaccumulatedin CD44-overexpressing cells. Conclusion: Apt-Dox conjugate selectively delivers doxorubicin to CD44-expressing cancer cells, thereby inhibiting selective cell proliferation and enhancing the targeted therapy.

Cargo-specific recruitment in clathrin- and dynamin-independent endocytosis.

Spatially controlled, cargo-specific endocytosis is essential for development, tissue homeostasis and cancer invasion. Unlike cargo-specific clathrin-mediated endocytosis, the clathrin- and dynamin-independent endocytic pathway (CLIC-GEEC, CG pathway) is considered a bulk internalization route for the fluid phase, glycosylated membrane proteins and lipids. While the core molecular players of CG-endocytosis have been recently defined, evidence of cargo-specific adaptors or selective uptake of proteins for the pathway are lacking. Here we identify the actin-binding protein Swiprosin-1 (Swip1, EFHD2) as a cargo-specific adaptor for CG-endocytosis. Swip1 couples active Rab21-associated integrins with key components of the CG-endocytic machinery-Arf1, IRSp53 and actin-and is critical for integrin endocytosis. Through this function, Swip1 supports integrin-dependent cancer-cell migration and invasion, and is a negative prognostic marker in breast cancer. Our results demonstrate a previously unknown cargo selectivity for the CG pathway and a role for specific adaptors in recruitment into this endocytic route.

P-225: A first-in-human study of FOR46 in patients with triple refractory Multiple Myeloma

<h3>Background</h3> Cluster of differentiation 46 (CD46) is highly expressed in multiple myeloma, especially in patients (pts) with gain of chromosome 1q and in the refractory setting. In vitro studies show upregulation and enhanced cytotoxicity upon treatment with pomalidomide, dexamethasone or lenalidomide. FOR46, an anti-CD46 antibody-drug conjugate with vc-MMAE, recognizes a tumor selective epitope of CD46 and is taken up by malignant cells by macropinocytosis, which is a relatively tumor selective uptake mechanism. <h3>Methods</h3> Pts with MM were enrolled who had progressed on proteasome inhibitors, immunomodulatory drugs and CD38-targeted therapies. An accelerated titration followed by 3+3 dose escalation design was used. FOR46, at protocol specified doses, was infused intravenously over 30-60 minutes on Day 1 of 21-day cycles. Following excess toxicity (neutropenia and fatigue) in a patient (pt) with high body mass index (BMI), dosing was changed from actual weight (AW) to adjusted body weight (ABW). G-CSF secondary prophylaxis was required for pts experiencing grade (gr) ≥ 3 neutropenia during a previous treatment cycle. The initial protocol had 2.4 mg/kg AW as the highest dose. When the MTD was not defined using ABW dosing, escalation was held pending protocol amendment to allow a higher dose and expansion to 10 patients at 2.4 mg/kg ABW began. Safety was evaluated using CTCAE v5.0 and efficacy was evaluated per IMWG criteria. Dexamethasone was only allowed for infusion reaction prophylaxis. CD46 antigen density was determined on patient MM cells via flow cytometry. <h3>Results</h3> Fifteen pts were enrolled at 6 pre-defined dose levels from 0.1 to 2.4 mg/kg with 1 patient each at the 0.1, 0.3 and 0.6 mg/kg dose levels, 3 at 1.2 and 1.8 mg/kg and 6 at 2.4 mg/kg. Median age was 68 (range 33 – 79) with 4 females. Gain 1q was present in 9 pts, absent in 5 pts and unknown in 1. The median number of prior lines of therapy was 6 (range 3-17). The only dose-limiting toxicity (DLT) was gr 4 neutropenia in 1 high BMI patient dosed by AW. This was the only DLT among 6 pts at 2.4 mg/kg dosed by a mix of AW (n=3) and ABW (n=3). One of 3 at 2.4 mg/kg ABW had non-dose limiting gr 4 neutropenia. The most common related adverse event was gr 4 neutropenia in 3 pts (20%). One patient (6.7%) had gr 4 thrombocytopenia and 1 each (6.7%) had gr 3 AST elevation, neutropenia, anemia, nausea, and peripheral neuropathy (PN). Of the 6 response-evaluable pts in the 1.8 and 2.4 mg/kg cohorts, 3 had partial responses (PRs) lasting 21, 30, and 15 weeks, respectively. Of the PRs, 1 pt did not have gain of 1q21. In addition to the fifteen pts in dose escalation cohorts, 10 have been enrolled in an expansion cohort at 2.4 mg/kg by ABW. <h3>Conclusion</h3> FOR46 demonstrates an acceptable toxicity profile using ABW dosing. There is encouraging evidence of efficacy in triple refractory MM. A protocol amendment allowing additional dose escalation to 2.7 mg/kg by ABW has been approved. NCT03650491

Targeting Cancer Cells Overexpressing Folate Receptors with New Terpolymer-Based Nanocapsules: Toward a Novel Targeted DNA Delivery System for Cancer Therapy.

Chemotherapeutics represent the standard treatment for a wide range of cancers. However, these agents also affect healthy cells, thus leading to severe off-target effects. Given the non-selectivity of the commonly used drugs, any increase in the selective tumor tissue uptake would represent a significant improvement in cancer therapy. Recently, the use of gene therapy to completely remove the lesion and avoid the toxicity of chemotherapeutics has become a tendency in oncotherapy. Ideally, the genetic material must be safely transferred from the site of administration to the target cells, without involving healthy tissues. This can be achieved by encapsulating genes into non-viral carriers and modifying their surface with ligands with high selectivity and affinity for a relevant receptor on the target cells. Hence, in this work we evaluate the use of terpolymer-based nanocapsules for the targeted delivery of DNA toward cancer cells. The surface of the nanocapsules is decorated with folic acid to actively target the folate receptors overexpressed on a variety of cancer cells. The nanocapsules demonstrate a good ability of encapsulating and releasing DNA. Moreover, the presence of the targeting moieties on the surface of the nanocapsules favors cell uptake, opening up the possibility of more effective therapies.

Engineering Mitochondriotropic Carbon Dots for Targeting Cancer Cells.

Aiming to understand and enhance the capacity of carbon dots (CDs) to transport through cell membranes and target subcellular organelles—in particular, mitochondria—a series of nitrogen-doped CDs were prepared by the one-step microwave-assisted pyrolysis of citric acid and ethylenediamine. Following optimization of the reaction conditions for maximum fluorescence, functionalization at various degrees with alkylated triphenylphosphonium functional groups of two different alkyl chain lengths afforded a series of functionalized CDs that exhibited either lysosome or mitochondria subcellular localization. Further functionalization with rhodamine B enabled enhanced fluorescence imaging capabilities in the visible spectrum and allowed the use of low quantities of CDs in relevant experiments. It was thus possible, by the appropriate selection of the alkyl chain length and degree of functionalization, to attain successful mitochondrial targeting, while preserving non-toxicity and biocompatibility. In vitro cell experiments performed on normal as well as cancer cell lines proved their non-cytotoxic character and imaging potential, even at very low concentrations, by fluorescence microscopy. Precise targeting of mitochondria is feasible with carefully designed CDs that, furthermore, are specifically internalized in cells and cell mitochondria of high transmembrane potential and thus exhibit selective uptake in malignant cells compared to normal cells.

Hydrogen Bond Strength-Mediated Self-Assembly of Supramolecular Nanogels for Selective and Effective Cancer Treatment.

This study provides a significant contribution to the development of multiple hydrogen-bonded supramolecular nanocarrier systems by demonstrating that controlling the hydrogen bond strength within supramolecular polymers represents a crucial factor to tailor the drug delivery performance and enhance the effectiveness of cancer therapy. Herein, we successfully developed two kinds of poly(ethylene glycol)-based telechelic polymers Cy-PEG and UrCy-PEG having self-constituted double and quadruple hydrogen-bonding cytosine (Cy) and ureido-cytosine (UrCy) end-capped groups, respectively, which directly assemble into spherical nanogels with a number of interesting physical characteristics in aqueous solutions. The UrCy-PEG nanogels containing quadruple hydrogen-bonded UrCy dimers exhibited excellent long-term structural stability in a serum-containing biological medium, whereas the double hydrogen-bonded Cy moieties could not maintain the structural integrity of the Cy-PEG nanogels. More importantly, after the drug encapsulation process, a series of in vitro experiments clearly confirmed that drug-loaded UrCy-PEG nanogels induced selective apoptotic cell death in cancer cells without causing significant cytotoxicity to healthy cells, while drug-loaded Cy-PEG nanogels exerted nonselective cytotoxicity toward both cancer and normal cells, indicating that increasing the strength of hydrogen bonds in nanogels plays a key role in enhancing the selective cellular uptake and cytotoxicity of drugs and the subsequent induction of apoptosis in cancer cells.

Sphingolipid metabolism during Toll-like receptor 4 (TLR4)-mediated macrophage activation.

Macrophage activation in response to stimulation of Toll-like receptor 4 (TLR4) provides a paradigm for investigating energy metabolism that regulates the inflammatory response. TLR4-mediated pro-inflammatory macrophage activation is characterized by increased glycolysis and altered mitochondrial metabolism, supported by selective amino acid uptake and/or usage. Fatty acid metabolism remains as a highly complex rewiring that accompanies classical macrophage activation. TLR4 activation leads to de novo synthesis of fatty acids, which flux into sphingolipids, complex lipids that form the building blocks of eukaryotic cell membranes and regulate cell function. Here, we review the importance of TLR4-mediated de novo synthesis of membrane sphingolipids in macrophages. We first highlight fatty acid metabolism during TLR4-driven macrophage immunometabolism. We then focus on the temporal dynamics of sphingolipid biosynthesis and emphasize the modulatory role of some sphingolipid species (i.e. sphingomyelins, ceramides and glycosphingolipids) on the pro-inflammatory and pro-resolution phases of LPS/TLR4 activation in macrophages.

Smart MSN-Drug-Delivery System for Tumor Cell Targeting and Tumor Microenvironment Release.

Tumor-targeted delivery and controlled release of antitumor drugs are promising strategies for increasing chemotherapeutic efficacy and reducing adverse effects. Although mesoporous silica nanoparticles (MSNs) have been known as a potential delivery system for doxorubicin (DOX), they have restricted applications due to their uncontrolled leakage and burst release from their large open pores. Herein, we engineered a smart drug-delivery system (smart MSN-drug) based on MSN-drug loading, cell membrane mimetic coating, on-demand pore blocking/opening, and tumor cell targeting strategies. The pore size of DOX-loaded MSNs was narrowed by polydopamine coating, and the pores/channels were blocked with tumor-targeting ligands anchored by tumor environment-rupturable -SS- chains. Furthermore, a cell membrane mimetic surface was constructed to enhance biocompatibility of the smart MSN-drug. Confocal microscopy results demonstrate highly selective uptake (12-fold in comparison with L929 cell) of the smart MSN-drug by HeLa cells and delivery into the HeLa cellular nuclei. Further in vitro IC50 studies showed that the toxicity of the smart MSN-drug to HeLa cells was 4000-fold higher than to the normal fibroblast cells. These exciting results demonstrate the utility of the smart MSN-drug capable of selectively killing tumor cells and saving the normal cells.

Coordinated action of multiple transporters in the acquisition of essential cationic amino acids by the intracellular parasite Toxoplasma gondii.

Intracellular parasites of the phylum Apicomplexa are dependent on the scavenging of essential amino acids from their hosts. We previously identified a large family of apicomplexan-specific plasma membrane-localized amino acid transporters, the ApiATs, and showed that the Toxoplasma gondii transporter TgApiAT1 functions in the selective uptake of arginine. TgApiAT1 is essential for parasite virulence, but dispensable for parasite growth in medium containing high concentrations of arginine, indicating the presence of at least one other arginine transporter. Here we identify TgApiAT6-1 as the second arginine transporter. Using a combination of parasite assays and heterologous characterisation of TgApiAT6-1 in Xenopus laevis oocytes, we demonstrate that TgApiAT6-1 is a general cationic amino acid transporter that mediates both the high-affinity uptake of lysine and the low-affinity uptake of arginine. TgApiAT6-1 is the primary lysine transporter in the disease-causing tachyzoite stage of T. gondii and is essential for parasite proliferation. We demonstrate that the uptake of cationic amino acids by TgApiAT6-1 is 'trans-stimulated' by cationic and neutral amino acids and is likely promoted by an inwardly negative membrane potential. These findings demonstrate that T. gondii has evolved overlapping transport mechanisms for the uptake of essential cationic amino acids, and we draw together our findings into a comprehensive model that highlights the finely-tuned, regulated processes that mediate cationic amino acid scavenging by these intracellular parasites.

Selective uptake of gaseous sulfur trioxide and mercury in ZnO-CuS composite at elevated temperatures from SO2-rich flue gas

Gaseous SO3 and mercury in the SO2-rich gas have aroused the complexity of multi-pollutants formation and are difficult for disposal. We here proposed a dry-flue gas purification method to capture these two pollutants above the SO3 boiling points (>180 °C), cutting off the downstream transformation. The selective uptake of SO3 and Hg0 at a high temperature from SO2-rich conditions is a challenge. The alkaline sorbent and chalcogen-based active sites were assembled to realize the induce-adsorption for SO3 and Hg0, respectively. The results indicated that the ZnO-CuS composite showed the feasibility for SO3 and Hg0 capture at elevated reaction temperatures. The composite with a molar ratio of 4:3 exhibited the highest performances for both Hg0 and SO3 uptake. ZnO has an excellent SO3 selectivity in SO3/SO2 atmosphere with a high SO3 adsorption energy of −466.5 kJ/mol. CuS was the leading active site for Hg0 adsorption using the surface Sn2− ions in Hg0/SO3/SO2 simulated flue gas. Moreover, the surface sulfation process inevitably happened, but the presence of Hg0 inhibited the reaction of SO3 with S2−, part of Hg0 adsorbed to generate HgS and HgSO4. The induced adsorption surface drove gaseous mercury to enter the inner of the material, widening the temperature window for efficient capture for gaseous mercury and enhancing adsorption stability. Moreover, a pilot-scale experiment using CuS and ZnO materials indicated that higher SO3 and total gaseous mercury removal efficiencies were obtained with the help of dust removal devices.

Multifunctional Coordination Polymer Exhibiting Reversible Mechanical Motion Allowing Selective Uptake of Guests and Leading to Enhanced Electrical Conductivity.

A remarkably flexible, multifunctional, 2D coordination polymer exhibiting an unprecedented mode of reversible mechanical motion, enabling pores to open and close, is reported. Such multifunctional materials are highly sought after, owing to the potential to exploit coexisting electronic and mechanical functionalities that underpin useful technological applications such as actuators and ultrasensitive detectors. The coordination polymer, of composition Mn(F4TCNQ)(py)2 (F4TCNQ = 2,3,5,6-tetrafluoro-7,7,8,8-tetracycanoquinodimethane; py = pyridine), consists of Mn(II) centers bridged by F4TCNQ dianions and coordinated by py molecules that extend above and below the 2D network. Exposure of Mn(F4TCNQ)(py)2, in its collapsed state, to carbon dioxide results in a pore-opening process at a threshold pressure for a given temperature. In addition to carbon dioxide, a variety of volatile guests may be incorporated into the pores, which are lined with electron-rich F4TCNQ dianions. The inclusion of electron-deficient guests such as 1,4-benzoquinone, nitrobenzene, maleic anhydride, and iodine into the pores is accompanied by a striking color change associated with a new host-guest charge-transfer interaction and an improvement in the semiconductor behavior, with the iodine adduct showing an increase in conductivity of almost 5 orders of magnitude. Experimental and density functional theory calculations on this remarkable multifunctional material demonstrate a reduction in the optical band gap with increasing electron affinity of the guest.

Thrombocytopenia after meta-iodobenzylguanidine (MIBG) therapy in neuroblastoma patients may be caused by selective MIBG uptake via the serotonin transporter located on megakaryocytes

BackgroundThe therapeutic use of [131I]meta-iodobenzylguanidine ([131I]MIBG) is often accompanied by hematological toxicity, primarily consisting of severe and persistent thrombocytopenia. We hypothesize that this is caused by selective uptake of MIBG via the serotonin transporter (SERT) located on platelets and megakaryocytes. In this study, we have investigated whether in vitro cultured human megakaryocytes are capable of selective plasma membrane transport of MIBG and whether pharmacological intervention with selective serotonin reuptake inhibitors (SSRIs) may prevent this radiotoxic MIBG uptake.MethodsPeripheral blood CD34+ cells were differentiated to human megakaryocytic cells using a standardized culture protocol. Prior to [3H]serotonin and [125I]MIBG uptake experiments, the differentiation status of megakaryocyte cultures was assessed by flow cytometry. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to assess SERT and NET (norepinephrine transporter) mRNA expression. On day 10 of differentiation, [3H]serotonin and [125I]MIBG uptake assays were conducted. Part of the samples were co-incubated with the SSRI citalopram to assess SERT-specific uptake. HEK293 cells transfected with SERT, NET, and empty vector served as controls.ResultsIn vitro cultured human megakaryocytes are capable of selective plasma membrane transport of MIBG. After 10 days of differentiation, megakaryocytic cell culture batches from three different hematopoietic stem and progenitor cell donors showed on average 9.2 ± 2.4 nmol of MIBG uptake per milligram protein per hour after incubation with 10–7 M MIBG (range: 6.6 ± 1.0 to 11.2 ± 1.0 nmol/mg/h). Co-incubation with the SSRI citalopram led to a significant reduction (30.1%—41.5%) in MIBG uptake, implying SERT-specific uptake of MIBG. A strong correlation between the number of mature megakaryocytes and SERT-specific MIBG uptake was observed.ConclusionOur study demonstrates that human megakaryocytes cultured in vitro are capable of MIBG uptake. Moreover, the SSRI citalopram selectively inhibits MIBG uptake via the serotonin transporter. The concomitant administration of citalopram to neuroblastoma patients during [131I]MIBG therapy might be a promising strategy to prevent the onset of thrombocytopenia.