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1.
Nature ; 606(7915): 706-712, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35732759

RESUMO

To use natural gas as a feedstock alternative to coal and oil, its main constituent, methane, needs to be isolated with high purity1. In particular, nitrogen dilutes the heating value of natural gas and is, therefore, of prime importance for removal2. However, the inertness of nitrogen and its similarities to methane in terms of kinetic size, polarizability and boiling point pose particular challenges for the development of energy-efficient nitrogen-removing processes3. Here we report a mixed-linker metal-organic framework (MOF) membrane based on fumarate (fum) and mesaconate (mes) linkers, Zr-fum67-mes33-fcu-MOF, with a pore aperture shape specific for effective nitrogen removal from natural gas. The deliberate introduction of asymmetry in the parent trefoil-shaped pore aperture induces a shape irregularity, blocking the transport of tetrahedral methane while allowing linear nitrogen to permeate. Zr-fum67-mes33-fcu-MOF membranes exhibit record-high nitrogen/methane selectivity and nitrogen permeance under practical pressures up to 50 bar, removing both carbon dioxide and nitrogen from natural gas. Techno-economic analysis shows that our membranes offer the potential to reduce methane purification costs by about 66% for nitrogen rejection and about 73% for simultaneous removal of carbon dioxide and nitrogen, relative to cryogenic distillation and amine-based carbon dioxide capture.

2.
Angew Chem Int Ed Engl ; 63(26): e202318844, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38785268

RESUMO

The quest for effective technologies to reduce SO2 pollution is crucial due to its adverse effects on the environment and human health. Markedly, removing a ppm level of SO2 from CO2-containing waste gas is a persistent challenge, and current technologies suffer from low SO2/CO2 selectivity and energy-intensive regeneration processes. Here using the molecular building blocks approach and theoretical calculation, we constructed two porous organic polymers (POPs) encompassing pocket-like structures with exposed imidazole groups, promoting preferential interactions with SO2 from CO2-containing streams. Markedly, the evaluated POPs offer outstanding SO2/CO2 selectivity, high SO2 capacity, and an easy regeneration process, making it one of the best materials for SO2 capture. To gain better structural insights into the notable SO2 selectivity of the POPs, we used dynamic nuclear polarization NMR spectroscopy (DNP) and molecular modelling to probe the interactions between SO2 and POP adsorbents. The newly developed materials are poised to offer an energy-efficient and environment-friendly SO2 separation process while we are obliged to use fossil fuels for our energy needs.

3.
J Am Chem Soc ; 145(28): 15435-15442, 2023 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-37421307

RESUMO

Metal-organic frameworks (MOFs) have emerged as excellent platforms possessing tunable and controllable optical behaviors that are essential in high-speed and multichannel data transmission in optical wireless communications (OWCs). Here, we demonstrate a novel approach to achieving a tunable wide modulation bandwidth and high net data rate by engineering a combination of organic linkers and metal clusters in MOFs. More specifically, two organic linkers of different emission colors, but equal molecular length and connectivity, are successfully coordinated by zirconium and hafnium oxy-hydroxy clusters to form the desired MOF structures. The precise change in the interactions between these different organic linkers and metal clusters enables control over fluorescence efficiency and excited state lifetime, leading to a tunable modulation bandwidth from 62.1 to 150.0 MHz and a net data rate from 303 to 363 Mb/s. The fabricated color converter MOFs display outstanding performance that competes, and in some instances surpasses, those of conventional materials commonly used in light converter devices. Moreover, these MOFs show high practicality in color-pure wavelength-division multiplexing (WDM), which significantly improved the data transmission link capacity and security by the contemporary combining of two different data signals in the same path. This work highlights the potential of engineered MOFs as a game-changer in OWCs, with significant implications for future high-speed and secure data transmission.

4.
Plant Cell Physiol ; 63(12): 1890-1899, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-35475535

RESUMO

Sinapate esters, which are induced in plants under ultraviolet-B (UV-B) irradiation, have important roles not only in the protection against UV-B irradiation but also in the regulation of stomatal closure. Here, we speculated that sinapate esters would function in the stomatal closure of Arabidopsis thaliana in response to UV-B. We measured the stomatal aperture size of the wild-type (WT) and bright trichomes 1 (brt1) and sinapoylglucose accumulator 1 (sng1) mutants under UV-B irradiation; the latter two mutants are deficient in the conversion of sinapic acid to sinapoylglucose (SG) and SG to sinapoylmalate (SM), respectively. Both the brt1 and sng1 plants showed smaller stomatal apertures than the WT under normal light and UV-B irradiation conditions. The accumulation of SM and malate were induced by UV-B irradiation in WT and brt1 plants but not in sng1 plants. Consistently, exogenous malate application reduced UV-B-induced stomatal closure in WT, brt1 and sng1 plants. Nonetheless, levels of reactive oxygen species (ROS), nitric oxide (NO) and cytosolic Ca2+ were higher in guard cells of the sng1 mutant than in those of the WT under normal white light and UV-B irradiation, suggesting that disturbance of sinapate metabolism induced the accumulation of these signaling molecules that promote stomatal closure. Unexpectedly, exogenous sinapic acid application prevented stomatal closure of WT, brt1 and sng1 plants. In summary, we hypothesize that SG or other sinapate esters may promote the UV-B-induced malate accumulation and stomatal closure, whereas sinapic acid inhibits the ROS-NO pathway that regulates UV-B-induced cytosolic Ca2+ accumulation and stomatal closure.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Peróxido de Hidrogênio/metabolismo , Óxido Nítrico/metabolismo , Ésteres/metabolismo , Malatos/metabolismo , Cálcio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Estômatos de Plantas/fisiologia , Ácido Abscísico/metabolismo
5.
Chem Soc Rev ; 51(19): 8300-8350, 2022 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-36070414

RESUMO

Membrane-based separations have garnered considerable attention owing to their high energy efficiency, low capital cost, small carbon footprint, and continuous operation mode. As a class of highly porous crystalline materials with well-defined pore systems and rich chemical functionalities, metal-organic frameworks (MOFs) have demonstrated great potential as promising membrane materials over the past few years. Different types of MOF-based membranes, including polycrystalline membranes, mixed matrix membranes (MMMs), and nanosheet-based membranes, have been developed for diversified applications with remarkable separation performances. In this comprehensive review, we first discuss the general classification of membranes and outline the historical development of MOF-based membranes. Subsequently, particular attention is devoted to design strategies for MOF-based membranes, along with detailed discussions on the latest advances on these membranes for various gas and liquid separation processes. Finally, challenges and future opportunities for the industrial implementation of these membranes are identified and outlined with the intent of providing insightful guidance on the design and fabrication of high-performance membranes in the future.


Assuntos
Estruturas Metalorgânicas , Estruturas Metalorgânicas/química , Porosidade , Relação Estrutura-Atividade
6.
J Am Chem Soc ; 144(15): 6813-6820, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35412323

RESUMO

Mixed-matrix membranes (MMMs) based on luminescent metal-organic frameworks (MOFs) and emissive polymers with the combination of their unique advantages have great potential in separation science, sensing, and light-harvesting applications. Here, we demonstrate MMMs for the field of high-speed visible-light communication (VLC) using a very efficient energy transfer strategy at the interface between a MOF and an emissive polymer. Our steady-state and ultrafast time-resolved experiments, supported by high-level density functional theory calculations, revealed that efficient and ultrafast energy transfer from the luminescent MOF to the luminescent polymer can be achieved. The resultant MMMs exhibited an excellent modulation bandwidth of around 80 MHz, which is higher than those of most well-established color-converting phosphors commonly used for optical wireless communication. Interestingly, we found that the efficient energy transfer further improved the light communication data rate from 132 Mb/s of the pure polymer to 215 Mb/s of MMMs. This finding not only showcases the promise of the MMMs for high-speed VLC but also highlights the importance of an efficient and ultrafast energy transfer strategy for the advancement of data rates of optical wireless communication.

7.
Exp Mol Pathol ; 127: 104811, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35850229

RESUMO

Mallory-Denk bodies (MDBs) consist of intracellular aggregates of misfolded proteins in ballooned hepatocytes and serve as important markers of progression in certain liver diseases. Resident hepatic macrophage-mediated inflammation influences the development of chronic liver diseases and cancer. Here, the first systematic study of macrophages heterogeneity in mice was conducted to illustrate the pathogenesis of MDB formation using single-nucleus RNA sequencing (snRNA-seq). Furthermore, we provided transcriptional profiles of macrophages obtained from the fractionation of mouse liver tissues following chronic injury. We equally identified seven discrete macrophage subpopulations, each involved in specific cellular activated pathways such as basal metabolism, immune regulation, angiogenesis, and cell cycle regulation. Among these, a specific macrophage cluster (Cluster4), a subpopulation specifically expressing genes that regulate cell division and the cell cycle, was identified. Interestingly, we found that CCR2 was significantly induced in Cluster2, thereby inducing monocytes to migrate to macrophages to promote MDB pathogenesis. Thus, our study is the first to demonstrate the heterogeneity of macrophages associated with liver MDB formation in mice through single-cell resolution. This serves as the basis for further insights into the pathogenesis of liver MDB formation and molecular mechanisms of chronic liver disease progression.


Assuntos
Hepatopatias , Transcriptoma , Animais , Hepatócitos/metabolismo , Fígado/metabolismo , Hepatopatias/genética , Hepatopatias/patologia , Macrófagos/metabolismo , Corpos de Mallory/metabolismo , Camundongos
8.
Inorg Chem ; 61(28): 10661-10666, 2022 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-35771949

RESUMO

Edge-transitive nets are regarded as appropriate blueprints for the practice of reticular chemistry, and in particular, for the rational design and synthesis of functional metal-organic frameworks (MOFs). Among edge-transitive nets, type I edge-transitive nets have unique coordination figures, offering only one edge-transitive target for their associated expressed net-cBUs. Here, we report the reticulation of the binodal edge-transitive (6, 6)-c nia net in MOF chemistry, namely, the deliberate assembly of trinuclear aluminum clusters and 6-connected hexacarboxylate ligands into highly porous nia-MOFs. Further studies reveal that Al-nia-MOF-1 shows promising attributes as a storage media for oxygen (O2) at high-pressure adsorption studies.

9.
Proc Natl Acad Sci U S A ; 116(36): 17673-17682, 2019 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-31427507

RESUMO

Nuclear energy development has entered an unexpected second nuclear era, which is mainly driven by developing countries. Despite major efforts to pursue a safe nuclear energy system in the first nuclear era, severe nuclear accidents occurred. A basic problem is that we do not have an adequate understanding of nuclear safety. From the viewpoints of risk and the close coupling of technical and social factors, this paper reexamines the nature of nuclear safety and reviews how previous experts understood it. We also highlight the new challenges that we are likely to confront in the unexpected second nuclear era and clarify some of the refinements that need to be made to the concept of nuclear safety from a sociotechnical perspective. These include the following: 1) Risk decisions should be made based on integrating social and technical elements (i.e., "social rationality"); 2) risk needs to be controlled based on the "Wuli-Shili-Renli" framework; 3) systems thinking should be substituted for reductionism in risk assessment, and social mechanisms need to be combined to address uncertainties; and 4) public-centered risk communication should be established. This contribution can provide a theoretical foundation for improving our understanding of the nature of nuclear safety and for transforming the concept of nuclear safety in the unexpected second nuclear era.

10.
J Am Chem Soc ; 142(19): 8580-8584, 2020 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-32307988

RESUMO

Herein, we report a new light-harvesting mixed-ligand Zr(IV)-based metal-organic framework (MOF),with underlying fcu topology, encompassing the [Zr6(µ3-O)4(µ3-OH)4(O2C-)12] cluster and an equimolar mixture of thiadiazole- and benzimidazole-functionalized ligands. The successful integration of ligands with similar structural features but with notable chemical distinction afforded the attainment of a highly efficient energy transfer (ET). Notably, the very strong spectral overlap between the emission spectrum of benzimidazole (energy donor) and the absorption spectrum of thiadiazole (energy acceptor) provided an ideal platform to achieve very rapid (picosecond time scale) and highly efficient energy transfer (around 90% efficiency), as evidenced by time-resolved spectroscopy. Remarkably, the ultrafast time-resolved experiments quantified for the first time the anticipated close proximity of the two linkers with an average distance of 17 Å. This finding paves the way for the design and synthesis of periodic MOFs affording very efficient and fast ET to mimic natural photosynthetic systems.

11.
J Am Chem Soc ; 141(18): 7245-7249, 2019 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-30986055

RESUMO

A luminescent Zr(IV)-based metal-organic framework (MOF), with the underlying fcu topology, encompassing a π-conjugated organic ligand with a thiadiazole functionality, exhibits an unprecedented low detection limit of 66 nM for amines in aqueous solution. Markedly, this ultralow detection is driven by hydrogen-bonding interactions between the linker and the hosted amines. This observation is supported by density functional theory (DFT) calculations, which clearly corroborate the suppression of the twisting motion of thiadiazole core in the presence of amine, reducing significantly the nonradiative recombination pathways and subsequently enhancing the emission intensity. Credibly, nicotine regarded as a harmful chemical and bearing an amine pending group is also detected with high sensitivity, positioning this MOF as a potential sensor for practical environmental applications. This finding serves also as a benchmark to understand the sensing mechanism in MOFs.

12.
J Am Chem Soc ; 140(28): 8858-8867, 2018 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-29923711

RESUMO

Rational design and construction of metal-organic frameworks (MOFs) with intricate structural complexity are of prime importance in reticular chemistry. We report our latest addition to the design toolbox in reticular chemistry, namely the concept of merged nets based on merging two edge-transitive nets into a minimal edge-transitive net for the rational construction of intricate mixed-linker MOFs. In essence, a valuable net for design enclosing two edges (not related by symmetry) is rationally generated by merging two edge-transitive nets, namely (3,6)-coordinated spn and 6-coordinated hxg. The resultant merged-net, a (3,6,12)-coordinated sph net with net transitivity [32] enclosing three nodes and two distinct edges, offers potential for deliberate design of intricate mixed-linker MOFs. We report implementation of the merged-net approach for the construction of isoreticular rare-earth mixed-linker MOFs, sph-MOF-1 to -4, based on the assembly of 12-c hexanuclear carboxylate-based molecular building blocks (MBBs), displaying cuboctahedral building units, 3-c tritopic ligands, and 6-c hexatopic ligands. The resultant sph-MOFs represent the first examples of MOFs where the underlying net is merged from two 3-periodic edge-transitive nets, spn and hxg. Distinctively, the sph-MOF-3 represents the first example of a mixed-linker MOF to enclose both trigonal and hexagonal linkers. The merged-nets approach allows the logical practice of isoreticular chemistry by taking into account the mathematically correlated dimensions of the two ligands to afford the deliberate construction of a mixed-linker mesoporous MOF, sph-MOF-4. The merged-net equation and two key parameters, ratio constant and MBB constant, are disclosed. A merged-net strategy for the design of mixed-linker MOFs by strictly controlling the size ratio between edges is introduced.

13.
Angew Chem Int Ed Engl ; 54(45): 13241-4, 2015 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-26305107

RESUMO

The porphyrin boxes (PB-1 and PB-2), which are rationally designed porous organic cages with a large cavity using well-defined and rigid 3-connected triangular and 4-connected square shaped building units are reported. PB-1 has a cavity as large as 1.95 nm in diameter and shows high chemical stability in a broad pH range (4.8 to 13) in aqueous media. The crystalline nature as well as cavity structure of the shape-persistent organic cage crystals were intact even after complete removal of guest molecules, leading to one of the highest surface areas (1370 m(2) g(-1)) among the known porous organic molecular solids. The size of the cavities and windows of the porous organic cages can be modulated using different sized building units while maintaining the topology of the cages, as illustrated with PB-2. Interestingly, PB-2 crystals showed unusual N2 sorption isotherms as well as high selectivity for CO2 over N2 and CH4 (201 and 47.9, respectively at 273 K at 1 bar).

14.
Chemistry ; 20(29): 9073-80, 2014 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-24919582

RESUMO

Three isoreticular metal-organic frameworks, JUC-100, JUC-103 and JUC-106, were synthesized by connecting six-node dendritic ligands to a [Zn4O(CO2)6] cluster. JUC-103 and JUC-106 have additional methyl and ethyl groups, respectively, in the pores with respect to JUC-100. The uptake measurements of the three MOFs for CH4, C2H4, C2H6 and C3H8 were carried out. At 298 K, 1 atm, JUC-103 has relatively high CH4 uptake, but JUC-100 is the best at 273 K, 1 atm. JUC-100 and JUC-103 have similar C2H4 absorption ability. In addition, JUC-100 has the best absorption capacity for C2H6 and C3H8. These results suggest that high surface area and appropriate pore size are important factors for gas uptake. Furthermore, ideal adsorbed solution theory (IAST) analyses show that all three MOFs have good C3H8/CH4 and C2H6/CH4 selectivities for an equimolar quaternary CH4/C2H4/C2H6/C3H8 gas mixture maintained at isothermal conditions at 298 K, and JUC-106 has the best C2H6/CH4 selectivity. The breakthrough simulations indicate that all three MOFs have good capability for separating C2 hydrocarbons from C3 hydrocarbons. The pulse chromatographic simulations also indicate that all three MOFs are able to separate CH4/C2 H4/C2H6/C3H8 mixture into three different fractions of C1, C2 and C3 hydrocarbons.

15.
Adv Mater ; 36(26): e2314206, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38517323

RESUMO

The separation of high-value-added chemicals from organic solvents is important for many industries. Membrane-based nanofiltration offers a more energy-efficient separation than the conventional thermal processes. Conceivably, mixed-matrix membranes (MMMs), encompassing metal-organic frameworks (MOFs) as fillers, are poised to promote selective separation via molecular sieving, synergistically combining polymers flexibility and fine-tuned porosity of MOFs. Nevertheless, conventional direct mixing of MOFs with polymer solutions results in underutilization of the MOF fillers owing to their uniform cross-sectional distribution. Therefore, in this work, a multizoning technique is proposed to produce MMMs with an asymmetric-filler density, in which the MOF fillers are distributed only on the surface of the membrane, and a seamless interface at the nanoscale. The design strategy demonstrates five times higher MOF surface coverage, which results in a solvent permeance five times higher than that of conventional MMMs while maintaining high selectivity. Practically, MOFs are paired with polymers of similar chemical nature to enhance their adhesion without the need for surface modification. The approach offers permanently accessible MOF porosity, which translates to effective molecular sieving, as exemplified by the polybenzimidazole and Zr-BI-fcu-MOF system. The findings pave the way for the development of composite materials with a seamless interface.

16.
Adv Mater ; 35(25): e2300296, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37045553

RESUMO

Membrane technology, regarded as an environmentally friendly and sustainable approach, offers great potential to address the large energy penalty associated with the energy-intensive propylene/propane separation. Quest for molecular sieving membranes for this important separation is of tremendous interest. Here, a fluorinated metal-organic framework (MOF) material, known as KAUST-7 (KAUST: King Abdullah University of Science and Technology) with well-defined narrow 1D channels that can effectively discriminate propylene from propane based on a size-sieving mechanism, is successfully incorporated into a polyimide matrix to fabricate molecular sieving mixed matrix membranes (MMMs). Markedly, the surface functionalization of KAUST-7 nanoparticles with carbene moieties affords the requisite interfacial compatibility, with minimal nonselective defects at polymer-filler interfaces, for the fabrication of a molecular sieving MMM. The optimal membrane with a high MOF loading (up to 45 wt.%) displays a propylene permeability of ≈95 barrer and a mixed propylene/propane selectivity of ≈20, far exceeding the state-of-the-art upper bound limits. Moreover, the resultant membrane exhibits robust structural stability under practical conditions, including high pressures (up to 8 bar) and temperatures (up to 100 °C). The observed outstanding performance attests to the importance of surface engineering for the preparation and plausible deployment of high-performance MMMs for industrial applications.

17.
J Phys Chem B ; 127(8): 1819-1827, 2023 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-36807993

RESUMO

Structural modifications to molecular systems that lead to the control of photon emission processes at the interfaces between photoactive materials play a key role in the development of fluorescence sensors, X-ray imaging scintillators, and organic light-emitting diodes (OLEDs). In this work, two donor-acceptor systems were used to explore and reveal the effects of slight changes in chemical structure on interfacial excited-state transfer processes. A thermally activated delayed fluorescence (TADF) molecule was chosen as the molecular acceptor. Meanwhile, two benzoselenadiazole-core MOF linker precursors, Ac-SDZ and SDZ, with the presence and absence of a C≡C bridge, respectively, were carefully chosen as energy and/or electron-donor moieties. We found that the SDZ -TADF donor-acceptor system exhibited efficient energy transfer, as evidenced by steady-state and time-resolved laser spectroscopy. Furthermore, our results demonstrated that the Ac-SDZ-TADF system exhibited both interfacial energy and electron transfer processes. Femtosecond-mid-IR (fs-mid-IR) transient absorption measurements revealed that the electron transfer process takes place on the picosecond timescale. Time-dependent density functional theory (TD-DFT) calculations confirmed that photoinduced electron transfer occurred in this system and demonstrated that it takes place from C≡C in Ac-SDZ to the central unit of the TADF molecule. This work provides a straightforward way to modulate and tune excited-state energy/charge transfer processes at donor-acceptor interfaces.

18.
Immunobiology ; 227(6): 152285, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36240611

RESUMO

Incomplete Kawasaki Disease is a complex disease that often occurs in infants and has substantial coronary artery damage. Its pathogenesis is unclear and lacks specific diagnostic markers. The purpose of our study is to research the mechanism of incomplete Kawasaki Disease use of bioinformatic methods and identify potential biomarkers. We performed weighted gene co-expression network analysis to analyze the data set GSE68004 and identified modules and genes which were correlated with the disease. Through functional annotation and enrichment analysis, we determined the biological function and signal pathway of these genes. We further used lasso regression and ROC curve to screen genes and determined that the final candidate gene was HSPB11and hsa-miR-155-5p that regulates its expression. Finally, we validated the screened gene using an independent dataset and construct a TF-miRNA network. Through the relationships of TFs and hsa-miR-155-5p, we found is hsa-miR-155-5p closely related to hypoxia-related transcription factors, which may be a new direction in the research of Kawasaki disease.


Assuntos
MicroRNAs , Síndrome de Linfonodos Mucocutâneos , Humanos , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Síndrome de Linfonodos Mucocutâneos/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Biologia Computacional/métodos , Biomarcadores , Fatores de Transcrição/genética , Redes Reguladoras de Genes
19.
Front Immunol ; 13: 925217, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35795680

RESUMO

Therapeutic tumor vaccines have become an important breakthrough in the treatment of various solid tumors including lung cancer. Dendritic cells (DCs)-based tumor vaccines targeting tumor-associated antigens (TAAs) play a key role in immunotherapy and immunoprevention. However, the weak immunogenicity of TAAs and low immune response rates are a major challenge faced in the application of therapeutic tumor vaccines. Here, we tested whether targeting an attractive target Mesothelin (MSLN) and PD-L1 immune checkpoint molecule to DCs in vivo would elicit therapeutic antitumor cytotoxic T lymphocyte (CTL) response. We generated specific MSLN fragment combined with PD-L1 and GM-CSF peptide immunogen (MSLN-PDL1-GMCSF) based on the novel anti-PD-L1 vaccination strategy we recently developed for the cancer treatment and prevention. We found that DCs loaded with MSLN-PDL1-GMCSF vaccine elicited much stronger endogenous anti-PD-L1 antibody and T cell responses in immunized mice and that antigen specific CTLs had cytolytic activities against tumor cells expressing both MSLN and PD-L1. We demonstrated that vaccination with MSLN-PDL1-GMCSF potently inhibited the tumor growth of MSLN+ and PD-L1+ lung cancer cells, exhibiting a significant therapeutic anti-tumor potential. Furthermore, PD-1 blockade further improved the synergistic antitumor therapeutic efficacy of MSLN-PDL1-GMCSF vaccine in immunized mice. In summary, our data demonstrated for the first time that this PD-L1-containing MSLN therapeutic vaccine can induce persistent anti-PD-L1 antibody and CTL responses, providing an effective immunotherapeutic strategy for lung cancer immunotherapy by combining MSLN-PDL1-GMCSF vaccine and PD-1 blockade.


Assuntos
Vacinas Anticâncer , Neoplasias Pulmonares , Animais , Antígenos de Neoplasias , Fatores Imunológicos , Imunoterapia , Neoplasias Pulmonares/terapia , Mesotelina , Camundongos , Receptor de Morte Celular Programada 1
20.
Vaccines (Basel) ; 10(7)2022 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-35891256

RESUMO

Dendritic cells (DCs), as professional antigen-presenting cells (APCs), play a key role in the initiation and regulation of humoral and cellular immunity. DC vaccines loaded with different tumor-associated antigens (TAAs) have been widely used to study their therapeutic effects on cancer. A number of clinical trials have shown that DCs are safe as an antitumor vaccine and can activate certain anti-tumor immune responses; however, the overall clinical efficacy of DC vaccine is not satisfactory, so its efficacy needs to be enhanced. MUC1 is a TAA with great potential, and the immune checkpoint PD-L1 also has great potential for tumor treatment. Both of them are highly expressed on the surface of various tumors. In this study, we generated a novel therapeutic MUC1-Vax tumor vaccine based on the method of PD-L1-Vax vaccine we recently developed; this novel PD-L1-containing MUC1-Vax vaccine demonstrated an elevated persistent anti-PD-L1 antibody production and elicited a much stronger protective cytotoxic T lymphocyte (CTL) response in immunized mice. Furthermore, the MUC1-Vax vaccine exhibited a significant therapeutic anti-tumor effect, which significantly inhibited tumor growth by expressing a high MUC1+ and PD-L1+ level of LLC and Panc02 tumor cells, and prolonged the survival of cancer-bearing animals. Taken together, our study provides a new immunotherapy strategy for improving the cross-presentation ability of therapeutic vaccine, which may be applicable to pancreatic cancer, lung cancer and for targeting other types of solid tumors that highly express MUC1 and PD-L1.

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