共查询到20条相似文献,搜索用时 0 毫秒
1.
Dr. Ester Álvarez-Benedicto Dr. Zeru Tian Dr. Sumanta Chatterjee Dr. Domenico Orlando Dr. Minjeong Kim Erick D. Guerrero Dr. Xu Wang Dr. Daniel J. Siegwart 《Angewandte Chemie (International ed. in English)》2023,62(44):e202310395
Chimeric Antigen Receptor (CAR) T cell immunotherapy is revolutionizing treatment for patients suffering from B-cell lymphoma (BL). However, the current method of CAR T cell production is complicated and expensive, requiring collection of patient blood to enrich the T cell population, ex vivo engineering/activation, and quality assessment before the patient can receive the treatment. Herein we leverage Spleen Selective ORgan Targeted (SORT) Lipid Nanoparticles (LNPs) to produce CAR T cells in situ and bypass the extensive and laborious process currently used. Optimized Spleen SORT LNPs containing 10 % 18 : 1 PA transfected CD3+, CD8+, and CD4+ T cells in wild-type mice. Spleen SORT LNPs delivered Cre recombinase mRNA and CAR encoding mRNA to T cells in reporter mice and in a lymphoreplete B cell lymphoma model (respectively) after intravenous injection without the need for active targeting ligands. Moreover, in situ CAR T cells increased the overall survival of mice with a less aggressive form of B cell lymphoma. In addition, in situ transfected CAR T cells reduced tumor metastasis to the liver by increasing tumor infiltrating lymphocytes. Overall, these results offer a promising alternative method for CAR T cell production with pre-clinical potential to treat hematological malignancies. 相似文献
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Deborah Leckband 《Current Opinion in Colloid & Interface Science》2001,6(5-6):498-505
Molecular recognition is generally thought of in terms of bond formation between unique sites on host and complementary guest molecules, but recent studies have revealed new complexities in biological recognition at cell. Adhesion between cell surfaces similarly involves specific interactions between analogous ligands and receptors. Recent force measurements, however, suggest that cell adhesion proteins may bind via multiple interaction sites that can form in a sequential manner. Other studies further show that in some instances, the principal recognition event may not be receptor–ligand docking, but the assembly of a complex pattern of many receptors and ligands. 相似文献
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Juan Ma Shenqing Wang Chuanfang Zhao Xiliang Yan Quanzhong Ren Zheng Dong Jiahuang Qiu Yin Liu Qing'e Shan Ming Xu Bing Yan Sijin Liu 《Angewandte Chemie (International ed. in English)》2023,62(18):e202301059
Adjuvants stimulate the immune system to vigorously respond to a vaccine. While current adjuvants such as aluminum salts and oil-in-water emulsions have been used for decades, they do not generate broad and long-lasting responses in many vaccines. Consequently, more potent adjuvants are needed. Here, using computer-aided molecule design and machine learning, we discovered 2 new, broad-spectrum adjuvants that can boost vaccine responses. Our library containing 46 toll-like receptor (TLR)-targeting agonist ligands were assembled on Au nanoparticles. Comprehensive in vitro, ex vivo and in vivo studies showed both leads promoted dendritic cell activation via multiple TLRs and enhanced antigen presentation to T cells. When used together with tumor-specific antigens to immunize mice against B16-OVA melanoma and 4T1-PD1 breast cancer, both adjuvants unleashed strong immune responses that suppressed tumor growth and lung metastases. Our results show computer-aided design and screening can rapidly uncover potent adjuvants for tackling waning immunity in current vaccines. 相似文献
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Wenxin Zhu Jinrun Dong Guoxiang Ruan Yuan Zhou Prof. Jiandong Feng 《Angewandte Chemie (International ed. in English)》2023,62(7):e202214419
A single-molecule electrochemiluminescence bioassay is developed here which allows imaging and direct quantification of single biomolecules. Imaging single biomolecules is realized by localizing the electrochemiluminescence events of the labeled molecules. Such an imaging system allows mapping the spatial distribution of biomolecules with electrochemiluminescence and contains quantitative single-molecule insights. We further quantify biomolecules by spatiotemporally merging the repeated reactions at one molecule site and then counting the clustered molecules. The proposed single-molecule electrochemiluminescence bioassay is used to detect carcinoembryonic antigen, showing a limit of detection of 67 attomole concentration which is 10 000 times better than conventional electrochemiluminescence bioassays. This spatial resolution and sensitivity enable single-molecule electrochemiluminescence bioassay a new toolbox for both specific bioimaging and ultrasensitive quantitative analysis. 相似文献
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Narinder SinghDoo Ok Jang 《Tetrahedron letters》2011,52(20):2608-2610
An imine linked fluorescent receptor for AMP has been synthesized with both hydrogen bond donor and hydrogen bond acceptor motifs as recognition sites in the design of a receptor. The receptor recognizes AMP selectively over a number of tested anions and biomolecules such as ADP and ATP, as illustrated through fluorescent enhancement. 相似文献
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Summary Two programs, OVID and SUPER, for exploring the similarity of molecules with respect to their action at a receptor are described. OVID accepts two molecules as input and optimizes the three-dimensional overlap of specified atoms in one molecule with specified atoms in the second molecule. The result is expressed as a percent of the theoretical maximum. OVID gives a quantitative measure of the extent of a guessed correspondence between two molecules based on volume overlap of selected atoms. The Achilles' heel of OVID is that the correspondence between the two molecules has to be guessed. We realized that it would be better to systematically examine all possible correspondences of two structures to minimize the chance of overlooking a superior correspondence. We created SUPER to satisfy this need. SUPER accepts two molecules as input and finds the top twenty correspondences of their surfaces and charge distributions, giving a quantitative measure of the extent of each correspondence. An instructive example of the application of OVID and SUPER to the design of leukotriene D4 receptor antagonists is described. SUPER appears to be a practical brainstorming tool for the medicinal chemist trying to understand how molecules whose structures may not resemble one another in an obvious way can bind to the same site. 相似文献
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In this review, the basic principles and apparatus of ECL imaging were briefly introduced at first. Then several latest and representative applications of ECL imaging based on nanomaterials and micro-/nanostructures were overviewed. Finally, the superiorities and challenges in ECL imaging for further development were discussed. 相似文献
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Lars Kröger 《Journal of carbohydrate chemistry》2013,32(7):717-722
Natural O‐glycoproteins such as the Thomsen‐Friedenreich antigen or gangliosides contain the motif Galβ1‐3GalNAc as an important disaccharide with significant biologic activity. The arrangement of spatial functionalities in this structure are of particular interest with regard to the development of potential leads en route to pharmaceuticals. Therefore, it was desired to obtain access to a range of modified derivatives of the aforementioned motif paying particular attention to introducing specific deoxy functions instead of hydroxyl groups. 相似文献
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Julie Descamps Dr. Camille Colin Prof. Gilles Tessier Dr. Stéphane Arbault Prof. Neso Sojic 《Angewandte Chemie (International ed. in English)》2023,62(16):e202218574
Here we report on a label-free electrochemiluminescence (ECL) microscopy using exceptionally low concentrations of the [Ru(bpy)3]2+ luminophore. This work addresses the central point of the minimal concentration of the ECL luminophore required to image single entities. We demonstrate the possibility to record ECL images of cells and mitochondria at concentrations down to nM and pM. This is 7 orders of magnitude lower than classically-used concentrations and corresponds to a few hundreds of luminophores diffusing around the biological entities. Yet, it produces remarkably sharp negative optical contrast ECL images, as demonstrated by structural similarity index metric analyses and supported by predictions of the ECL image covering time. Finally, we show that the reported approach is a simple, fast, and highly sensitive method, which opens new avenues for ultrasensitive ECL imaging and ECL reactivity at the single molecule level. 相似文献
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Electrochemiluminescence (ECL) is a kind of luminescent phenomenon caused by electrochemical reactions. Based on the advantages of ECL including low background, high sensitivity, strong spatiotemporal controllability and simple operation, ECL imaging is able to visualize the ECL process, which can additionally achieve high throughput, fast and visual analysis. With the development of optical imaging technique, ECL imaging at micro- or nanoscale has been successfully applied in immunoassay, cell imaging, biochemical analysis, single-nanoparticle detection and study of mechanisms and kinetics of reactions, which has attracted extensive attention. In this review, the basic principles and apparatus of ECL imaging were briefly introduced at first. Then several latest and representative applications of ECL imaging based on nanomaterials and micro-/nanostructures were overviewed. Finally, the superiorities and challenges in ECL imaging for further development were discussed. 相似文献
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Benjamin P. M. Lake Dr. Ryan G. Wylie Dr. Cyril Bařinka Dr. Anthony F. Rullo 《Angewandte Chemie (International ed. in English)》2023,62(9):e202214659
Chemical immunotherapeutic strategies including Antibody Recruiting Molecules (ARMs - bivalent small molecules containing an antibody-binding domain (ABD) and a target-binding domain (TBD)) direct immune-mediated clearance of diseased cells. Anti-cancer ARM function relies on high tumor antigen valency, limiting function against lower antigen expressing tumors. To address this limitation, we report a tunable multivalent immune recruitment (MIR) platform to amplify/stabilize antibody recruitment to cells with lower antigen valencies. An initial set of polymeric ARMs (pARMs) were synthesized and screened to evaluate ABD/TBD copy number, ratio, and steric occlusion on specific immune induction. Most pARMs demonstrated simultaneous high avidity binding to anti-dinitrophenyl antibodies and prostate-specific membrane antigens on prostate cancer. Optimized pARMs mediated enhanced anti-cancer immune function against lower antigen expressing target cells compared to an analogous ARM. 相似文献
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Ryo Kato 《Tetrahedron letters》2004,45(22):4273-4276
Potential use of a surfactant-like receptor is demonstrated at the 1,2-dichloroethane-water interface for strong and selective binding of H2PO4− over Br− and Cl−. The analysis by interfacial tensiometry reveals that the interfacial adsorption of a thiourea-isothiouronium conjugate, BT-C1, is significantly stabilized by the binding of H2PO4− with the adsorption constant of 1.7 × 105 M−1 while the interfacial adsorptivity of this receptor is relatively moderate for Br− (0.81 × 105 M−1) and Cl− (0.63 × 105 M−1). Such complexation-induced interfacial adsorption behaviors of BT-C1 are discussed as a basis for the development of receptor-based chemical sensors for phosphate anions. 相似文献
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Dr. Patrick Eiring Dr. Teresa Klein Dr. Simone Backes Marcel Streit Marvin Jungblut Dr. Sören Doose Dr. Gerti Beliu Prof. Dr. Markus Sauer 《Angewandte Chemie (International ed. in English)》2023,62(30):e202300821
The angiotensin-converting enzyme 2 (ACE2) has been identified as entry receptor on cells enabling binding and infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via trimeric spike (S) proteins protruding from the viral surface. It has been suggested that trimeric S proteins preferably bind to plasma membrane areas with high concentrations of possibly multimeric ACE2 receptors to achieve a higher binding and infection efficiency. Here we used direct stochastic optical reconstruction microscopy (dSTORM) in combination with different labeling approaches to visualize the distribution and quantify the expression of ACE2 on different cells. Our results reveal that endogenous ACE2 receptors are present as monomers in the plasma membrane with densities of only 1–2 receptors μm−2. In addition, binding of trimeric S proteins does not induce the formation of ACE2 oligomers in the plasma membrane. Supported by infection studies using vesicular stomatitis virus (VSV) particles bearing S proteins our data demonstrate that a single S protein interaction per virus particle with a monomeric ACE2 receptor is sufficient for infection, which provides SARS-CoV-2 a high infectivity. 相似文献
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从利用物理刺激和生物大分子诱导两个方面综述了人工调控细胞表面受体聚集状态的策略.前者是利用相应的纳米材料在光、磁场、温度等物理刺激作用下实现人工调控受体聚集;后者则利用包括蛋白/多肽类分子、核酸在内的生物分子的自组装对其靶向识别的受体进行人工调控.系统介绍了相关研究领域取得的最新进展,并阐述和展望了该领域现存的挑战和发展方向. 相似文献
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Daniele Pavo e Pavo Chirlene Nascimento Botelho Ridvan Nunes Fernandes Clenilton Costa dos Santos Flavio Santos Damos Rita de Cssia Silva Luz 《Electroanalysis》2020,32(7):1498-1506
Ciprofloxacin is an antibiotic that belongs to the class of drugs known as quinolones and it is frequently used to treat a variety of bacterial infections. The present work aims the development of a simple, cost‐effective, and environmentally friendly method for the determination of ciprofloxacin in drugs and artificial urine samples due to the high importance of this antibiotic for the human health. The proposed method is based on the electrogenerated chemiluminescence (ECL) resulting from the reaction between the ciprofloxacin and the tris(2,2′‐bipyridyl)ruthenium(II) complex. This method exploits a screen‐printed carbon electrode positioned in an ECL cell with capacity to 50 μL of electrolytic solution. The ECL intensity was monitored with the aid of a photodiode. The ECL signal was simultaneously registered to the voltammetric measurements. Under optimized experimental conditions, the ECL method presented a linear response range for ciprofloxacin between 0.5 and 500 μmol L?1 (or 0.0005 and 0.5 mmol L?1). The proposed method presented a detection limit of 0.5 μmol L?1 and it was successfully applied for the ciprofloxacin determination in drugs and artificial urine samples, with good accuracy and precision. 相似文献
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Xiyun Ye Dr. Peiyuan Zhang John C. K. Wang Dr. Corey L. Smith Silvino Sousa Dr. Andrei Loas Dr. Dan L. Eaton Dr. Magdalena Preciado López Prof. Dr. Bradley L. Pentelute 《Angewandte Chemie (International ed. in English)》2023,62(19):e202300289
α-Klotho, an aging-related protein found in the kidney, parathyroid gland, and choroid plexus, acts as an essential co-receptor with the fibroblast growth factor 23 receptor complex to regulate serum phosphate and vitamin D levels. Decreased levels of α-Klotho are a hallmark of age-associated diseases. Detecting or labeling α-Klotho in biological milieu has long been a challenge, however, hampering the understanding of its role. Here, we developed branched peptides by single-shot parallel automated fast-flow synthesis that recognize α-Klotho with improved affinity relative to their monomeric versions. These peptides were further shown to selectively label Klotho for live imaging in kidney cells. Our results demonstrate that automated flow technology enables rapid synthesis of complex peptide architectures, showing promise for future detection of α-Klotho in physiological settings. 相似文献
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将Eu(tta)3dpbt (dpbt: 2-(N,N-diethylanilin-4-yl)-4,6-bis(3,5-dimethylpyrazol-1-yl)-1,3,5-triazine; tta:thenoyltrifluoroacetonato)包埋在甲基丙烯酸甲酯-苯乙烯共聚物、正辛基三甲氧基硅及其水解缩合产物组成的杂化基质中, 制备了Eu(tta)3dpbt 质量分数为40%的荧光纳米粒子, 其平均粒径为45 nm. 所制备的发光纳米粒子在水中分散稳定性高、光稳定性好、细胞毒性低、长波敏化Eu3+发光性能优良, 适宜作为生物分析的发光标记物. 所制备的发光纳米粒子的可见区激发峰位于415 nm, 激发峰尾部延展至475 nm, 其发光量子产率为0.31(λex=415 nm, T=23 ℃), 最大双光子激发作用截面为5.0×105 GM (λex=830 nm, 1 GM=10-50 cm4·s·photo-1×particle-1). 以转铁蛋白修饰上述发光纳米粒子表面制备的纳米生物探针被成功应用于活的HeLa肿瘤细胞的特异性标记和双光子激发Eu3+发光成像. 相似文献