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151.
Selective Uptake of Cylindrical Poly(2‐Oxazoline) Brush‐AntiDEC205 Antibody‐OVA Antigen Conjugates into DEC‐Positive Dendritic Cells and Subsequent T‐Cell Activation 下载免费PDF全文
Dr. Jasmin Bühler Sabine Gietzen Dr. Anika Reuter Cinja Kappel Dr. Karl Fischer Sandra Decker David Schäffel Dr. Kaloian Koynov Dr. Matthias Bros Ingrid Tubbe Dr. Stephan Grabbe Dr. Manfred Schmidt 《Chemistry (Weinheim an der Bergstrasse, Germany)》2014,20(39):12405-12410
To achieve specific cell targeting by various receptors for oligosaccharides or antibodies, a carrier must not be taken up by any of the very many different cells and needs functional groups prone to clean conjugation chemistry to derive well‐defined structures with a high biological specificity. A polymeric nanocarrier is presented that consists of a cylindrical brush polymer with poly‐2‐oxazoline side chains carrying an azide functional group on each of the many side chain ends. After click conjugation of dye and an anti‐DEC205 antibody to the periphery of the cylindrical brush polymer, antibody‐mediated specific binding and uptake into DEC205+‐positive mouse bone marrow‐derived dendritic cells (BMDC) was observed, whereas binding and uptake by DEC205? negative BMDC and non‐DC was essentially absent. Additional conjugation of an antigen peptide yielded a multifunctional polymer structure with a much stronger antigen‐specific T‐cell stimulatory capacity of pretreated BMDC than application of antigen or polymer–antigen conjugate. 相似文献
152.
Magnetobiosensors Based on Viral Protein p19 for MicroRNA Determination in Cancer Cells and Tissues 下载免费PDF全文
Dr. Susana Campuzano Dr. Eva López‐Hernández Felipe Conzuelo Dr. Rosario Granados Dr. José M. Sánchez‐Puelles Prof. José M. Pingarrón 《Angewandte Chemie (International ed. in English)》2014,53(24):6168-6171
MicroRNAs (miRs) have emerged as important clinical biomarkers with both diagnostic and prognostic value for relevant diseases, such as cancer. MiRs pose unique challenges for detection and are currently detected by northern blotting, real‐time PCR, and microarray techniques. These expensive, complicated, and time‐consuming techniques are not feasible for on‐site miR determination. In this study, amperometric magnetobiosensors involving RNA‐binding viral protein p19 as a selective biorecognition element were developed for miR quantification. The p19‐based magnetosensors were able to detect 0.4 fmol of a synthetic target and endogenous miR‐21 (selected as a model for its role in a wide variety of cancers) in only 2 h in total RNA extracted from cancer cells and human breast‐tumor specimens without PCR amplification and sample preprocessing. These results open up formidable perspectives for the diagnosis and prognosis of human cancers and for drug‐discovery programs. 相似文献
153.
Combinatorially Designed Lipid‐like Nanoparticles for Intracellular Delivery of Cytotoxic Protein for Cancer Therapy 下载免费PDF全文
Dr. Ming Wang Kyle Alberti Shuo Sun Carlos Luis Arellano Prof. Dr. Qiaobing Xu 《Angewandte Chemie (International ed. in English)》2014,53(11):2893-2898
An efficient and safe method to deliver active proteins into the cytosol of targeted cells is highly desirable to advance protein‐based therapeutics. A novel protein delivery platform has been created by combinatorial design of cationic lipid‐like materials (termed “lipidoids”), coupled with a reversible chemical protein engineering approach. Using ribonuclease A (RNase A) and saporin as two representative cytotoxic proteins, the combinatorial lipidoids efficiently deliver proteins into cancer cells and inhibit cell proliferation. A study of the structure–function relationship reveals that the electrostatic and hydrophobic interactions between the lipidoids and the protein play a vital role in the formation of protein–lipidoid nanocomplexes and intracellular delivery. A representative lipidoid (EC16‐1) protein nanoparticle formulation inhibits cell proliferation in vitro and suppresses tumor growth in a murine breast cancer model. 相似文献
154.
Discovery of Cell‐Permeable Inhibitors That Target the BRCT Domain of BRCA1 Protein by Using a Small‐Molecule Microarray 下载免费PDF全文
Zhenkun Na Sijun Pan Dr. Mahesh Uttamchandani Prof. Dr. Shao Q. Yao 《Angewandte Chemie (International ed. in English)》2014,53(32):8421-8426
BRCTs are phosphoserine‐binding domains found in proteins involved in DNA repair, DNA damage response and cell cycle regulation. BRCA1 is a BRCT domain‐containing, tumor‐suppressing protein expressed in the cells of breast and other human tissues. Mutations in BRCA1 have been found in ca. 50 % of hereditary breast cancers. Cell‐permeable, small‐molecule BRCA1 inhibitors are promising anticancer agents, but are not available currently. Herein, with the assist of microarray‐based platforms, we have discovered the first cell‐permeable protein–protein interaction (PPI) inhibitors against BRCA1. By targeting the (BRCT)2 domain, we showed compound 15 a and its prodrug 15 b inhibited BRCA1 activities in tumor cells, sensitized these cells to ionizing radiation‐induced apoptosis, and showed synergistic inhibitory effect when used in combination with Olaparib (a small‐molecule inhibitor of poly‐ADP‐ribose polymerase) and Etoposide (a small‐molecule inhibitor of topoisomerase II). Unlike previously reported peptide‐based PPI inhibitors of BRCA1, our compounds are small‐molecule‐like and could be directly administered to tumor cells, thus making them useful for future studies of BRCA1/PARP‐related pathways in DNA damage and repair response, and in cancer therapy. 相似文献
155.
Artificial Accelerators of the Molecular Chaperone Hsp90 Facilitate Rate‐Limiting Conformational Transitions 下载免费PDF全文
Bettina K. Zierer Matthias Weiwad Martin Rübbelke Lee Freiburger Gunter Fischer Oliver R. Lorenz Michael Sattler Klaus Richter Johannes Buchner 《Angewandte Chemie (International ed. in English)》2014,53(45):12257-12262
The molecular chaperone Hsp90 undergoes an ATP‐driven cycle of conformational changes in which large structural rearrangements precede ATP hydrolysis. Well‐established small‐molecule inhibitors of Hsp90 compete with ATP‐binding. We wondered whether compounds exist that can accelerate the conformational cycle. In a FRET‐based screen reporting on conformational rearrangements in Hsp90 we identified compounds. We elucidated their mode of action and showed that they can overcome the intrinsic inhibition in Hsp90 which prevents these rearrangements. The mode of action is similar to that of the co‐chaperone Aha1 which accelerates the Hsp90 ATPase. However, while the two identified compounds influence conformational changes, they target different aspects of the structural transitions. Also, the binding site determined by NMR spectroscopy is distinct. This study demonstrates that small molecules are capable of triggering specific rate‐limiting transitions in Hsp90 by mechanisms similar to those in protein cofactors. 相似文献
156.
Dr. Shan Sun Qiao Chen Zhongdi Tang Chuang Liu Prof. Zhongjun Li Prof. Aiguo Wu Prof. Hengwei Lin 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2020,132(47):21227-21234
A method is developed to fabricate tumor microenvironment (TME) stimuli-responsive nanoplatform for fluorescence (FL) imaging and synergistic cancer therapy via assembling photosensitizer (chlorine e6, Ce6) modified carbon dots (CDs-Ce6) and Cu2+. The as-obtained nanoassemblies (named Cu/CC nanoparticles, NPs) exhibit quenched FL and photosensitization due to the aggregation of CDs-Ce6. Their FL imaging and photodynamic therapy (PDT) functions are recovered efficiently once they entering tumor sites by the stimulation of TME. Introducing of Cu2+ not only provides extra chemodynamic therapy (CDT) function through reaction with hydrogen peroxide (H2O2), but also depletes GSH in tumors by a redox reaction, thus amplifying the intracellular oxidative stress and enhancing the efficacy of reactive oxygen species (ROS) based therapy. Cu/CC NPs can act as a FL imaging guided trimodal synergistic cancer treatment agent by photothermal therapy (PTT), PDT, and thermally amplified CDT. 相似文献
157.
Shaojun Yang Qiao Tang Long Chen Jin Chang Tian Jiang Jingyi Zhao Prof. Ming Wang Prof. Peng R. Chen 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2020,132(41):18243-18250
The abundance of bacterial effectors have inspired us to explore their potential in rewiring malignant cell signaling. Their incapability for entering cells, however, hinders such application. Herein we developed a cationic lipid-based high throughput library screening platform for effective intracellular delivery of bacterial effectors. As the misregulated MAPK signaling is a hallmark of many types of cancer, we turned to the Shigella effector OspF which irreversibly inactivates ERK, the terminal component of MAPK cascade. We created a function-based screening assay to obtain AMPA-O16B lipid nanoparticles for effective OspF intracellular delivery, which inhibited the malignant MAPK signaling and tumor growth in vitro and in vivo. Furthermore, the optimized lipid nanoparticle formulation can deliver OspF to modulate the immunosuppressive responses in macrophages. Our work is a general strategy to explore the therapeutic potentials of naturally evolved bacterial effectors. 相似文献
158.
Soodabeh Davaran Mohammad Sadeghinia Zahra Jamalpoor Vahideh Raeisdasteh Hokmabad Mehdi Doosti-Telgerd Ansar Karimian Zahra Sadeghinia Javad Khalilifard Akram keramt Farzad Moradikhah Ali Sadeghinia 《Electrophoresis》2020,41(12):1081-1094
Microfluidic system, or lab-on-a-chip, has grown explosively. This system has been used in research for the first time and then entered in the clinical section. Due to economic reasons, this technique has been used for screening of laboratory and clinical indices. The microfluidic system solves some difficulties accompanied by clinical and biological applications. In this review, the interpretation and analysis of some recent developments in microfluidic systems in biomedical applications with more emphasis on tissue engineering and cancer will be discussed. Moreover, we try to discuss the features and functions of microfluidic systems. 相似文献
159.
Dr. Qing Li Shenhua Li Dr. Shasha He Wan Chen Penghui Cheng Dr. Yan Zhang Prof. Qingqing Miao Prof. Kanyi Pu 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2020,132(18):7084-7089
Discriminative detection of invasive and noninvasive breast cancers is crucial for their effective treatment and prognosis. However, activatable probes able to do so in vivo are rare. Herein, we report an activatable polymeric reporter (P-Dex) that specifically turns on near-infrared (NIR) fluorescent and photoacoustic (PA) signals in response to the urokinase-type plasminogen activator (uPA) overexpressed in invasive breast cancer. P-Dex has a renal-clearable dextran backbone that is linked with a NIR dye caged with an uPA-cleavable peptide substrate. Such a molecular design allows P-Dex to passively target tumors, activate NIR fluorescence and PA signals to effectively distinguish invasive MDA-MB-231 breast cancer from noninvasive MCF-7 breast cancer, and ultimately undergo renal clearance to minimize the toxicity potential. Thus, this polymeric reporter holds great promise for the early detection of malignant breast cancer. 相似文献
160.
开发了一条合成天然产物Uncinine的新方法,基于此设计合成了一系列新型的丁烯内酯衍生物.通过噻唑蓝(MTT)法评价了目标化合物对胃癌细胞的增殖抑制活性,分析了其构效关系.其中,3-吗啉甲基-4-(4-叔丁基苯基)亚基丁烯内酯(9l)对MGC803的IC50为2.9μmol/L,对胃癌细胞MGC803、HGC27以及SGC7901具有明显的选择性增殖抑制作用,而对正常的胃粘膜上皮细胞GES1具有较小的毒性.初步的作用机制研究表明,化合物9l诱导胃癌细胞MGC803凋亡依赖Caspase 9/3激活. 相似文献