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排序方式: 共有547条查询结果,搜索用时 15 毫秒
541.
Zhiming Cheng Dr. Emily J Thompson Dr. Lorena Mendive-Tapia Dr. Jamie I Scott Dr. Sam Benson Dr. Takanori Kitamura Ana Senan-Salinas Dr. Youhani Samarakoon Dr. Edward W Roberts Dr. Maykel A Arias Prof. Dr. Julian Pardo Dr. Eva M Galvez Prof. Dr. Marc Vendrell 《Angewandte Chemie (International ed. in English)》2023,62(8):e202216142
Cytotoxic immune cells, including T lymphocytes (CTLs) and natural killer (NK) cells, are essential components of the host response against tumors. CTLs and NK cells secrete granzyme A (GzmA) upon recognition of cancer cells; however, there are very few tools that can detect physiological levels of active GzmA with high spatiotemporal resolution. Herein, we report the rational design of the near-infrared fluorogenic substrates for human GzmA and mouse GzmA. These activity-based probes display very high catalytic efficiency and selectivity over other granzymes, as shown in tissue lysates from wild-type and GzmA knock-out mice. Furthermore, we demonstrate that the probes can image how adaptive immune cells respond to antigen-driven recognition of cancer cells in real time. 相似文献
542.
Dr. Liu-Yi Liu Tian-Zhu Ma You-Liang Zeng Dr. Wenting Liu Dr. Hang Zhang Prof. Dr. Zong-Wan Mao 《Angewandte Chemie (International ed. in English)》2023,62(36):e202305645
G-quadruplexes (G4s) have been revived as promising therapeutic targets with the development of immunotherapy, but the G4-mediated immune response remains unclear. We designed a novel class of G4-binding organic-platinum hybrids, L1-cispt and L1-transpt , with spatial matching for G4 binding and G4 DNA reactivity for binding site locking. The solution structure of L1-transpt -MYT1L G4 demonstrated the effectiveness of the covalent binding and revealed the covalent binding-guided dynamic balance, accompanied by the destruction of the A5-T17 base pairs to achieve the covalent binding of the platinum unit to N7 of the G6 residue. Furthermore, L1-cispt- and L1-transpt- mediated genomic dysfunction could activate the retinoic acid-induced gene I (RIG-I) pathway and induce immunogenic cell death (ICD). The use of L1-cispt/L1-transpt- treated dying cells as therapeutic vaccines stimulated a robust immune response and effectively inhibited tumor growth in vivo. Our findings highlight the importance of the rational combination of specific spatial recognition and covalent locking in G4-trageting drug design and their potential in immunotherapy. 相似文献
543.
Peixin Guan Zhanchen Guo Dr. Shuxin Xu Dr. Haifeng Lu Prof. Lisheng Wang Zikuan Gu Prof. Zhen Liu 《Angewandte Chemie (International ed. in English)》2023,62(17):e202301202
Harnessing innate immunity is an appealing strategy for cancer treatment. Herein, we report a new strategy called molecularly imprinted nanobeacons (MINBs) for redirecting innate immune killing towards triple-negative breast cancer (TNBC). The MINBs were molecularly imprinted nanoparticles with the N-epitope of glycoprotein nonmetastatic B (GPNMB) as the template and grafted with plentiful fluorescein moieties as the hapten. The MINBs could tag the TNBC cells via binding with GPNMB and thereby provide navigation for recruiting hapten-specific antibodies. The gathered antibodies could further trigger effective Fc-domain-mediated immune killing towards the tagged cancer cells. In vivo experiments showed that the TNBC growth was significantly inhibited after MINBs treatment by intravenous injection as compared with control groups. This study not only opens a new access for redirecting innate immunity towards TNBC but also paves the way for innate immunity-based therapy of other diseases. 相似文献
544.
Dr. Wen Su Dr. Mixiao Tan Zhihang Wang Jie Zhang Wenping Huang Haohao Song Xinye Wang Prof. Haitao Ran Prof. Yanfeng Gao Prof. Guangjun Nie Prof. Hai Wang 《Angewandte Chemie (International ed. in English)》2023,62(11):e202218128
Proteolysis targeting chimeras (PROTACs) technology is an emerging approach to degrade disease-associated proteins. Here, we report carbon-dot (CD)-based PROTACs (CDTACs) that degrade membrane proteins via the ubiquitin-proteasome system. CDTACs can bind to programmed cell death ligand 1 (PD-L1), recruit cereblon (CRBN) to induce PD-L1 ubiquitination, and degrade them with proteasomes. Fasting-mimicking diet (FMD) is also used to enhance the cellular uptake and proteasome activity. More than 99 % or 90 % of PD-L1 in CT26 or B16-F10 tumor cells can be degraded by CDTACs, respectively. Furthermore, CDTACs can activate the stimulator of interferon genes (STING) pathway to trigger immune responses. Thus, CDTACs with FMD treatment effectively inhibit the growth of CT26 and B16-F10 tumors. Compared with small-molecule-based PROTACs, CDTACs offer several advantages, such as efficient membrane protein degradation, targeted tumor accumulation, immune system activation, and in vivo detection. 相似文献
545.
Delivering alternative strategies to deal with cancer is a huge milestone in research. Cancer cells can give a senescence response as consequence of cellular stress or external stimuli such as the use of chemotherapies, which could end up eventually in cancer relapse. Controlling cellular senescence will surely open new cancer treatment approaches. Cancer senescence induction can be used as an added timeframe to look for alternative treatments and senolytic drugs to avoid cancer relapse destroying the senescent cells (SnCs). Within cancer senescence research, metal complexes are underdeveloped in comparison with that of organic molecules or nanoparticles. Herein, we highlight the scarce investigation performed with metal complexes in the field of senescence and how a great input on them could be a huge step towards the search of alternative cancer treatments. 相似文献
546.
《Arabian Journal of Chemistry》2023,16(2):104514
1,4-Dihydropyridine is a privileged scaffold present in many bioactive molecules, from coenzymes to commercially available drugs. Among other interesting properties, it has been found good anticancer activity in some of these 1,4-DHPs, therefore many research groups are trying to develop new compounds based on this structural core.For this purpose, in this work, a family of 23 new 1,4-dihydropyridines has been synthesized using hydrazide and malononitrile derivatives as precursors. This straightforward catalytic process has given rise to the desired products with moderate to excellent yields. All the compounds have been tested against four different cancer cell lines [HeLa (human cervical carcinoma), Jurkat (leukemia), A549 (human lung cancer) and MIA PaCa-2 (pancreatic cancer)] to establish a preliminary structure–activity relationship. From this study, and among the best candidates, we chose 4-chlorophenyl and 4-(trifluoromethyl)phenyl derivatives in the malononitrile ring to synthesize a second generation of molecules with enhanced cytotoxicity, modifying the substituent in the N-heterocyclic position (acylhydrazine moieties). With this second generation of compounds, we successfully decreased the IC50 until 7 µM.An in-depth analysis of their biological properties suggests that these promising compounds trigger a non-conventional cell death mechanism known as paraptosis. Moreover, the tested photophysical properties of these products show in some cases an interesting long wavelength emission and excitation, potentially leading to new biosensors or theragnostic agents.Finally, in vivo assays concerning the acute toxicity in mice of two of the most active compounds (with an alkyl chain of seven carbon atoms in the acylhydrazine moiety) demonstrated that even dosed at thousands fold the corresponding IC50 values (2500 and 3300 times more concentrated than the IC50 values for the two compounds studied), there was no sign of harmful effects on the tested subjects, results that support their use in further studies to discover new anticancer drugs. 相似文献
547.
To enhance the porosity and accessibility, a novel drug carrier, the hollow core zeolitic-imidazolate framework-8 (HZIF-8), is designed using polystyrene as a hard template to sequentially load and release 5-fluorouracil (FU). HZIF-8 is signified by a large surface area and pore volume, reaching 1727.1 m2/g and 0.99 cm3/g, respectively. The obtained HZIF-8 exhibits rhombic dodecahedron morphology with a uniform particle size of 450 nm. The integrated hollow core is observed at ca. 180 nm. Evaluation of the FU encapsulation behavior in HZIF-8 nanospheres is demonstrated via the adsorption kinetics, isotherm, and thermodynamic studies. The maximum FU uptake is monitored at 40 °C with the loading capacity of 161.9 mg/g. This study suggests that the FU uptake follows the pseudo-second-order law and multilayer mechanism. The governing mechanism is chemical binding in its first layer and physical interaction in the upper layers. The release study of FU from FU-loaded HZIF-8 shows that the cumulative release at pH 5.5 (92.03%) is four times higher than that at pH 7.4 (23.31%), indicating a stimulus-responsive release mechanism where pH is required as an internal stimulus factor. 相似文献