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1.
Xinjian Yang Zhenhua Li Meng Li Prof. Jinsong Ren Prof. Xiaogang Qu 《Chemistry (Weinheim an der Bergstrasse, Germany)》2013,19(45):15378-15383
A multifunctional system for intracellular drug delivery and simultaneous fluorescent imaging was constructed by using histidine‐tagged, cyan fluorescent protein (CFP)‐capped magnetic mesoporous silica nanoparticles (MMSNs). This protein‐capped multifunctional nanostructure is highly biocompatible and does not affect cell viability or proliferation. The CFP acts not only as a capping agent, but also as a fluorescent imaging agent. The nanoassembly was activated by histidine‐based replacement, leading to release of drug molecules encapsulated in the nanopores into the bulk solution. The fluorescent imaging functionality would allow noninvasive tracking of the nanoparticles in the body. By combining the drug delivery with cell‐imaging capability, these nanoparticles may provide valuable multifunctional nanoplatforms for biomedical applications. 相似文献
2.
Yuyan Jiang Jingchao Li Ziling Zeng Chen Xie Yan Lyu Kanyi Pu 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2019,131(24):8245-8249
Despite its great potential in cancer treatment, photodynamic therapy (PDT) often exacerbates hypoxia and subsequently compromises its therapeutic efficacy. To overcome this issue, an organic photodynamic nanoinhibitor (OPNi) has been synthesized that has the additional ability to counteract carbonic anhydrase IX (CA‐IX), a molecular target in the hypoxia‐mediated signalling cascade. OPNi is composed of a metabolizable semiconducting polymer as the photosensitizer and a CA‐IX antagonist conjugated amphiphilic polymer as the matrix. This molecular structure allows OPNi not only to selectively bind CA‐IX positive cancer cells to facilitate its tumor accumulation but also to regulate the CA‐IX‐related pathway. The integration of CA‐IX inhibition into the targeted PDT process eventually has a synergistic effect, leading to superior antitumor efficacy over that of PDT alone, as well as the reduced probability of hypoxia‐induced cancer metastasis. This study thus proposes a molecular strategy to devise simple yet amplified photosensitizers to conquer the pitfalls of traditional PDT. 相似文献
3.
Kathrin Butzbach Federico A.O. Rasse‐Suriani M. Micaela Gonzalez Franco M. Cabrerizo Bernd Epe 《Photochemistry and photobiology》2016,92(4):611-619
Photodynamic therapy (PDT) is based on the cytotoxicity of photosensitizers in the presence of light. Increased selectivity and effectivity of the treatment is expected if a specific uptake of the photosensitizers into the target cells, often tumor cells, can be achieved. An attractive transporter for that purpose is the folic acid receptor α (FRα), which is overexpressed on the surface of many tumor cells and mediates an endocytotic uptake. Here, we describe the synthesis and photobiological characterization of polar β‐carboline derivatives as photosensitizers covalently linked to folate‐tagged albumin as the carrier system. The particles were taken up by KB (human carcinoma) cells within <90 min and then co‐localized with a lysosomal marker. FRα antibodies prevented the uptake and also the corresponding conjugate without folate was not taken up. Accordingly, a folate‐albumin‐β‐carbolinium conjugate proved to be phototoxic, while the corresponding albumin–β‐carbolinium conjugates without FA were nontoxic, both with and without irradiation. An excess of free folate as competitor for the FRα‐mediated uptake completely inhibited the photocytotoxicity. Interestingly, the albumin conjugates are devoid of photodynamic activity under cell‐free conditions, as shown for DNA as a target. Thus, phototoxicity requires cellular uptake and lysosomal degradation of the conjugates. In conclusion, albumin–folate conjugates appear to be promising vehicles for a tumor cell targeted PDT. 相似文献
4.
Surendar R. Jakka Vijayakumar Govindaraj Govindasamy Mugesh 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2019,131(23):7795-7799
Direct delivery of proteins into mammalian cells is a challenging problem in biological and biomedical applications. The most common strategies for the delivery of proteins into the cells include the use of cell‐penetrating peptides or supercharged proteins. Herein, we show for the first time that a single atom change, hydrogen to halogen, at one of the tyrosine residues can increase the cellular entry of ~28 kDa green fluorescent protein (GFP) in mammalian cells. The protein uptake is facilitated by a receptor‐mediated endocytosis and the cargo can be released effectively into cytosol by co‐treatment with the endosomolytic peptide ppTG21. 相似文献
5.
Mussel‐Inspired Protein Nanoparticles Containing Iron(III)–DOPA Complexes for pH‐Responsive Drug Delivery
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Dr. Bum Jin Kim Hogyun Cheong Dr. Byeong Hee Hwang Prof. Hyung Joon Cha 《Angewandte Chemie (International ed. in English)》2015,54(25):7318-7322
A novel bioinspired strategy for protein nanoparticle (NP) synthesis to achieve pH‐responsive drug release exploits the pH‐dependent changes in the coordination stoichiometry of iron(III)–3,4‐dihydroxyphenylalanine (DOPA) complexes, which play a major cross‐linking role in mussel byssal threads. Doxorubicin‐loaded polymeric NPs that are based on FeIII–DOPA complexation were thus synthesized with a DOPA‐modified recombinant mussel adhesive protein through a co‐electrospraying process. The release of doxorubicin was found to be predominantly governed by a change in the structure of the FeIII–DOPA complexes induced by an acidic pH value. It was also demonstrated that the fabricated NPs exhibited effective cytotoxicity towards cancer cells through efficient cellular uptake and cytosolic release. Therefore, it is anticipated that FeIII–DOPA complexation can be successfully utilized as a new design principle for pH‐responsive NPs for diverse controlled drug‐delivery applications. 相似文献
6.
Adriano F. Lima Fernanda G. Basso Ana P. D. Ribeiro Vanderlei S. Bagnato Josimeri Hebling Giselle M. Marchi Carlos A. de Souza Costa 《Photochemistry and photobiology》2014,90(1):201-206
The aim of this study was to evaluate the effect of low‐level laser therapy (LLLT) on odontoblast‐like cells exposed to a bleaching agent. Mouse dental papilla cell‐23 cells were seeded in wells of 24‐well plates. Eight groups were established according to the exposure to the bleaching agent and LLLT (0, 4, 10 and 15 J cm?2). Enamel–dentin disks were adapted to artificial pulp chambers, which were individually placed in wells containing Dulbecco's modified Eagle's medium (DMEM). A bleaching agent (35% hydrogen peroxide [BA35%HP]) was applied on enamel (15 min) to obtain the extracts (DMEM + BA35%HP components diffused through enamel/dentin disks). The extracts were applied (1 h) to the cells, and then subjected to LLLT. Cell viability (Methyl tetrazolium assay), alkaline phosphatase (ALP) activity, as well as gene expression of ALP, fibronectin (FN) and type I collagen, were evaluated. The bleaching procedures reduced the cell viability, ALP activity and gene expression of dentin proteins. Laser irradiation did not modulate the cell response; except for FN, as LLLT decreased the gene expression of this protein by the cells exposed to the BA35%HP. It can be concluded that BA35%HP decreased the activities of odontoblasts that were not recovered by the irradiation of the damaged cells with low‐level laser parameters tested. 相似文献
7.
Amrita Mukhopadhyay Christin Grabinski A. R. M. Nabiul Afrooz Navid B. Saleh Saber Hussain 《Applied biochemistry and biotechnology》2012,167(2):327-337
Gold nanoparticles exhibit unique spectral properties that make them ideal for biosensing, imaging, drug delivery, and other therapeutic applications. Interaction of gold nanoparticles within biological environments is dependent on surface characteristics, which may rely on particular capping agents. In this study, gold nanospheres (GNS) synthesized with different capping agents??specifically citric acid (CA) and tannic acid (TA)??were compared for serum protein adsorption and cellular uptake into a lung epithelial cell line (A549). Both GNS samples exhibited noticeable protein adsorption based on surface charge data after exposure to serum proteins. Light scattering measurements revealed that GNS-CA-protein composites were smaller and less dense compared to GNS-TA-protein composites. The cell uptake characteristics of these nanoparticles were also different. GNS-CA formed large clusters and elicited high uptake, while GNS-TA were taken up as discrete particles, possibly through nonendosomal mechanisms. These results indicate that the capping agents used for GNS synthesis result in unique biological interactions. 相似文献
8.
Bright,Highly Water‐Soluble Triazacyclononane Europium Complexes To Detect Ligand Binding with Time‐Resolved FRET Microscopy
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Martina Delbianco Dr. Victoria Sadovnikova Emmanuel Bourrier Dr. Gérard Mathis Dr. Laurent Lamarque Dr. Jurriaan M. Zwier Prof. David Parker 《Angewandte Chemie (International ed. in English)》2014,53(40):10718-10722
Luminescent europium complexes are used in a broad range of applications as a result of their particular emissive properties. The synthesis and application of bright, highly water‐soluble, and negatively charged sulfonic‐ or carboxylic acid derivatives of para‐substituted aryl–alkynyl triazacyclononane complexes are described. Introduction of the charged solubilizing moieties suppresses cellular uptake or adsorption to living cells making them applicable for labeling and performing assays on membrane receptors. These europium complexes are applied to monitor fluorescent ligand binding on cell‐surface proteins with time‐resolved Förster resonance energy transfer (TR‐FRET) assays in plate‐based format and using TR‐FRET microscopy. 相似文献
9.
《化学:亚洲杂志》2017,12(1):122-129
We report the construction of a non‐toxic nanoassembly of bovine serum albumin (BSA) protein and the cucurbit[7]uril macrocycle as well as its stimuli‐responsive breakage with adamantylamine or pH, which restores the protein structure and recognition properties. The assembly showed efficient loading and controlled release of a standard drug, doxorubicin (DOX), and the same was validated in live cells. The cell viability studies documented that the DOX‐loaded assembly mask the cytotoxicity of DOX and the toxicity can be revived at the target on demand, triggering its therapeutic activation. This is found to be more effective in the cancer cells. In addition, such host‐assisted protein assemblies are also highly promising for stabilizing/protecting the native protein structure, a viable approach to prevent/inhibit protein misfolding and aggregation. 相似文献
10.
Markus Leimbacher Dr. Yixin Zhang Dr. Luca Mannocci Michael Stravs Dr. Tim Geppert Dr. Jörg Scheuermann Prof. Gisbert Schneider Prof. Dario Neri 《Chemistry (Weinheim an der Bergstrasse, Germany)》2012,18(25):7729-7737
Libraries of chemical compounds individually coupled to encoding DNA tags (DNA‐encoded chemical libraries) hold promise to facilitate exceptionally efficient ligand discovery. We constructed a high‐quality DNA‐encoded chemical library comprising 30 000 drug‐like compounds; this was screened in 170 different affinity capture experiments. High‐throughput sequencing allowed the evaluation of 120 million DNA codes for a systematic analysis of selection strategies and statistically robust identification of binding molecules. Selections performed against the tumor‐associated antigen carbonic anhydrase IX (CA IX) and the pro‐inflammatory cytokine interleukin‐2 (IL‐2) yielded potent inhibitors with exquisite target specificity. The binding mode of the revealed pharmacophore against IL‐2 was confirmed by molecular docking. Our findings suggest that DNA‐encoded chemical libraries allow the facile identification of drug‐like ligands principally to any protein of choice, including molecules capable of disrupting high‐affinity protein–protein interactions. 相似文献
11.
Martina Delbianco Victoria Sadovnikova Emmanuel Bourrier Grard Mathis Laurent Lamarque Jurriaan M. Zwier David Parker 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2014,126(40):10894-10898
Luminescent europium complexes are used in a broad range of applications as a result of their particular emissive properties. The synthesis and application of bright, highly water‐soluble, and negatively charged sulfonic‐ or carboxylic acid derivatives of para‐substituted aryl–alkynyl triazacyclononane complexes are described. Introduction of the charged solubilizing moieties suppresses cellular uptake or adsorption to living cells making them applicable for labeling and performing assays on membrane receptors. These europium complexes are applied to monitor fluorescent ligand binding on cell‐surface proteins with time‐resolved Förster resonance energy transfer (TR‐FRET) assays in plate‐based format and using TR‐FRET microscopy. 相似文献
12.
A Potent Glucose–Platinum Conjugate Exploits Glucose Transporters and Preferentially Accumulates in Cancer Cells
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Dr. Malay Patra Dr. Timothy C. Johnstone Dr. Kogularamanan Suntharalingam Prof. Stephen J. Lippard 《Angewandte Chemie (International ed. in English)》2016,55(7):2550-2554
Three rationally designed glucose–platinum conjugates (Glc–Pts) were synthesized and their biological activities evaluated. The Glc–Pts, 1 – 3 , exhibit high levels of cytotoxicity toward a panel of cancer cells. The subcellular target and cellular uptake mechanism of the Glc–Pts were elucidated. For uptake into cells, Glc–Pt 1 exploits both glucose and organic cation transporters, both widely overexpressed in cancer. Compound 1 preferentially accumulates in and annihilates cancer, compared to normal epithelial, cells in vitro. 相似文献
13.
Stiti M Cecchi A Rami M Abdaoui M Barragan-Montero V Scozzafava A Guari Y Winum JY Supuran CT 《Journal of the American Chemical Society》2008,130(48):16130-16131
An approach for the synthesis of carbonic anhydrase (CA, EC 4.2.1.1) inhibitor coated gold nanoparticles is reported. This nanomaterial selectively inhibited the tumor-associated isoform CA IX overexpressed in hypoxic cancers over the ubiquitous, cytosolic housekeeping isozymes CA I and II and was membrane impermeant. As CA IX has an extracellular active site, the new nanomaterial which is confined to the extracellular space may be useful for imaging and treatment of hypoxic tumors. 相似文献
14.
Hao-Dong Cui De-Hong Hu Jing-Nan Zhang Guan-Hui Gao Cui-Fang Zheng Ping Gong Xing-Hua Xi Zong-Hai Sheng Lin-Tao Cai 《中国化学快报》2017,28(7):1391-1398
As one of near-infrared (NIR) fluorescent (FL) nanoprobes, gold nanoclusters (Au NCs) are delicated to passive-targeting tumors for NIR FL imaging, but which easily cleared by the kidneys for the small size (<1.5 nm). Herein, the well-defined gold clusters nanoassembly (Au CNA) was synthesized by the selfassembly of Au NCs based on protein cross-linking approach. The as-prepared Au CNA demonstrated highly effective cellular uptake and precise tumor targeting compared to that of Au NCs. Moreover, with the irradiation of 660 nm laser, Au CNA generated largely reactive oxygen species (ROS) for photodynamic therapy (PDT). In vitro and in vivo PDT revealed that Au CNA exhibited largely cell death and significantly tumor removal at a low power density of 0.2 W/cm2. It could be speculated that the laser-excited Au CNA produced photon energy, which further obtained electron from oxygen to generate radical species. Therefore, Au CNA as a photosensitizer could realize NIR FL imaging and NIR laser induced PDT. 相似文献
15.
In Situ Proteome Profiling and Bioimaging Applications of Small‐Molecule Affinity‐Based Probes Derived From DOT1L Inhibitors
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Biwei Zhu Dr. Hailong Zhang Sijun Pan Chenyu Wang Dr. Jingyan Ge Prof. Dr. Jun‐Seok Lee Prof. Dr. Shao Q. Yao 《Chemistry (Weinheim an der Bergstrasse, Germany)》2016,22(23):7824-7836
DOT1L is the sole protein methyltransferase that methylates histone H3 on lysine 79 (H3K79), and is a promising drug target against cancers. Small‐molecule inhibitors of DOT1L such as FED1 are potential anti‐cancer agents and useful tools to investigate the biological roles of DOT1L in human diseases. FED1 showed excellent in vitro inhibitory activity against DOT1L, but its cellular effect was relatively poor. In this study, we designed and synthesized photo‐reactive and “clickable” affinity‐based probes (AfBPs), P1 and P2 , which were cell‐permeable and structural mimics of FED1 . The binding and inhibitory effects of these two probes against DOT1L protein were extensively investigated in vitro and in live mammalian cells (in situ). The cellular uptake and sub‐cellular localization properties of the probes were subsequently studied in live‐cell imaging experiments, and our results revealed that, whereas both P1 and P2 readily entered mammalian cells, most of them were not able to reach the cell nucleus where functional DOT1L resides. This offers a plausible explanation for the poor cellular activity of FED1 . Finally with P1 / P2 , large‐scale cell‐based proteome profiling, followed by quantitative LC‐MS/MS, was carried out to identify potential cellular off‐targets of FED1 . Amongst the more than 100 candidate off‐targets identified, NOP2 (a putative ribosomal RNA methyltransferase) was further confirmed to be likely a genuine off‐target of FED1 by preliminary validation experiments including pull‐down/Western blotting (PD/WB) and cellular thermal shift assay (CETSA). 相似文献
16.
Daisy M. Ramos Sama Abdulmalik Michael R. Arul Swetha Rudraiah Cato T. Laurencin Augustus D. Mazzocca Sangamesh G. Kumbar 《先进技术聚合物》2019,30(5):1205-1215
Use of growth factors as biochemical molecules to elicit cellular differentiation is a common strategy in tissue engineering. However, limitations associated with growth factors, such as short half‐life, high effective physiological doses, and high costs, have prompted the search for growth factor alternatives, such as growth factor mimics and other proteins. This work explores the use of insulin protein as a biochemical factor to aid in tendon healing and differentiation of cells on a biomimetic electrospun micro‐nanostructured scaffold. Dose response studies were conducted using human mesenchymal stem cells (MSCs) in basal media supplemented with varied insulin concentrations. A dose of 100‐ng/mL insulin showed increased expression of tendon markers. Synthetic‐natural blends of various ratios of polycaprolactone (PCL) and cellulose acetate (CA) were used to fabricate micro‐nanofibers to balance physicochemical properties of the scaffolds in terms of mechanical strength, hydrophilicity, and insulin delivery. A 75:25 ratio of PCL:CA was found to be optimal in promoting cellular attachment and insulin immobilization. Insulin immobilized fiber matrices also showed increased expression of tendon phenotypic markers by MSCs similar to findings with insulin supplemented media, indicating preservation of insulin bioactivity. Insulin functionalized scaffolds may have potential applications in tendon healing and regeneration. 相似文献
17.
Cross‐Linked Aptamer–Lipid Micelles for Excellent Stability and Specificity in Target‐Cell Recognition
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Xiaowei Li Dr. C. Adrian Figg Dr. Ruowen Wang Dr. Ying Jiang Dr. Yifan Lyu Hao Sun Dr. Yuan Liu Dr. Yanyue Wang Dr. I‐Ting Teng Dr. Weijia Hou Dr. Ren Cai Dr. Cheng Cui Long Li Xiaoshu Pan Prof. Brent S. Sumerlin Prof. Weihong Tan 《Angewandte Chemie (International ed. in English)》2018,57(36):11589-11593
The specific binding ability of DNA–lipid micelles (DLMs) can be increased by the introduction of an aptamer. However, supramolecular micellar structures based on self‐assemblies of amphiphilic DLMs are expected to demonstrate low stability when interacting with cell membranes under certain conditions, which could lead to a reduction in selectivity for targeting cancer cells. We herein report a straightforward cross‐linking strategy that relies on a methacrylamide branch to link aptamer and lipid segments. By an efficient photoinduced polymerization process, covalently linked aptamer–lipid units help stabilize the micelle structure and enhance aptamer probe stability, further improving the targeting ability of the resulting nanoassembly. Besides the development of a facile cross‐linking method, this study clarifies the relationship between aptamer–lipid concentration and the corresponding binding ability. 相似文献
18.
Fujun Yang Qingyu Ji Rui Liao Shumeng Li Yuequan Wang Xuanbo Zhang Shenwu Zhang Haotian Zhang Qiming Kan Jin Sun Zhonggui He Bingjun Sun Cong Luo 《中国化学快报》2022,33(4):1927-1932
Photodynamic therapy(PDT) has been widely investigated for cancer therapy. The intracellular accumulation of reactive oxygen species(ROS)-damaged protein facilitates tumor cell apoptosis. However, there is growing evidence that the ubiquitin-proteasome pathway(UPP) significantly impedes PDT by preventing the enrichment of ROS-damaged proteins in tumor cells. To tackle this challenge, we report a facile dual-drug nanoassembly based on the discovery of an interesting co-assembly of bortezomib(BTZ,... 相似文献
19.
《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2017,129(41):12788-12792
Stimuli‐responsive molecular containers are of great importance for controlled drug delivery and other biomedical applications. A new type of acid labile acyclic cucurbit[n ]uril (CB[n ]) molecular containers is presented that can degrade and release the encapsulated cargo at accelerated rates under mildly acidic conditions (pH 5.5–6.5). These containers retain the excellent recognition properties of CB[n ]‐type hosts. A cell culture study demonstrated that the cellular uptake of cargos could be fine‐tuned by complexation with different containers. The release and cell uptake of cargo dye was promoted by acidic pH. 相似文献
20.
Quantitative study of cellular heterogeneity in doxorubicin uptake and its pharmacological effect on cancer cells
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Bin Deng Zhi‐Ming Wang Zi‐Hao Zhou Yi‐Meng Liu Xi‐Liang Yang Jian Song Yu‐Xiu Xiao 《Biomedical chromatography : BMC》2014,28(10):1393-1401
Cellular heterogeneity in doxorubicin (DOX) uptake and its relationship with pharmacological effect on cancer cells were quantitatively investigated for the first time. An in vitro experimental model was established by treating human leukemia K562 and breast cancer MCF‐7 cells with different schedules of DOX with or without surface P‐glycoprotein (P‐gp) inhibitor verapamil (VER). The cellular heterogeneity in DOX uptake was quantitatively examined by single‐cell analysis using capillary electrophoresis coupled with laser‐induced fluorescence detection. The corresponding cytotoxic effect was tested by cellular morphology, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐tetrazolium and flow cytometry assays. The expression of cellular membrane surface P‐gp was determined by flow cytometry. Results showed that the cellular heterogeneity exists in DOX uptake. The single‐high DOX schedule leads to lower uptake heterogeneity and higher mean drug uptake. The cellular heterogeneity in DOX uptake was found to be negatively correlated with drug cytotoxicity and surface P‐gp expression, with r = ?0.7680 to ~ ?0.9587. VER reduces the cellular variation in DOX uptake, suggesting that surface P‐gp may be one of the causes of the cellular heterogeneity in DOX uptake. This research demonstrates the importance of quantitative study of cellular heterogeneity in drug uptake and its potential application in drug schedule design, response prediction and therapy modulation. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献