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Cell penetrating peptides

Yawei Xu, Yan Zhou, Rui Yin, Cheng Wang, Haijiao Chu, Junling Wang
The balance of oxidation and reduction in the body requires the synergistic effect of various antioxidant enzymes. Therefore, the construction of enzyme mimics with multiple antioxidant activities is important and beneficial for further research on the synergistic effects of antioxidant enzymes and their mechanism of action. To explore the synergistic effect of superoxide dismutase (SOD) and glutathione peroxidase (GPx), a 76-mer selenium-containing peptide (Se-76P) mimic containing the active SOD and GPx centers was designed...
March 20, 2018: In Vitro Cellular & Developmental Biology. Animal
A Held, A Glas, L Dietrich, M Bollmann, K Brandstädter, T N Grossmann, C H Lohmann, T Pap, J Bertrand
OBJECTIVE: The canonical Wnt signaling pathway has been shown to be involved in regulating chondrocyte hypertrophic differentiation during OA. The aim of this study was to test the therapeutic potential of two stapled peptide canonical Wnt inhibitors - SAH-Bcl9 and StAx-35R - in preventing Wnt induced cartilage changes in OA. METHODS: Primary neonatal murine chondrocytes and cartilage explants from OA patients undergoing total joint replacement for knee OA, were used for microscopy to determine matrix and cell penetrating capacity of FITC-tagged SAH-Bcl9 and StAx-35R peptides...
March 17, 2018: Osteoarthritis and Cartilage
Hai Xu, Xi Bao, Yiwei Wang, Yue Xu, Bihua Deng, Yu Lu, Jibo Hou
BACKGROUND: DNA delivery with bacteriophage by surface-displayed mammalian cell penetrating peptides has been reported. Although, various phages have been used to facilitate DNA transfer by surface displaying the protein transduction domain of human immunodeficiency virus type 1 Tat protein (Tat peptide), no similar study has been conducted using T7 phage. METHODS: In this study, we engineeredT7 phage as a DNA targeting delivery vector to facilitate cellular internalization...
March 20, 2018: Virology Journal
Celina Yang, Kyle Bromma, Devika Chithrani
Optimizing the interface between nanoparticles (NPs) and the biological environment at various levels should be considered for improving delivery of NPs to the target tumor area. For NPs to be successfully delivered to cancer cells, NPs needs to be functionalized for circulation through the blood vessels. In this study, accumulation of Polyethylene Glycol (PEG) functionalized gold nanoparticles (GNPs) was first tested using in vitro monolayer cells and multilayer cell models prior to in vivo models. A diameter of 10 nm sized GNP was selected for this study for sufficient penetration through tumor tissue...
March 20, 2018: Cancers
D P N Gonçalves, D M Park, T L Schmidt, C Werner
Glioblastoma multiforme (GBM) contains a population of tumor initiating stem-like cells, termed cancer stem cells (CSCs). These CSCs, which are resistant to chemo- and radiotherapy, are thought to persist after treatment and drive tumor recurrence. Thus, it is believed that the elimination of CSCs can lead to GBM remission. GBM CSCs express Nestin on their surface, and can be therefore targeted via this protein. Gold nanorods (AuNRs) functionalized with an engineered, modular peptide that recognizes Nestin (NesPEG-AuNRs) were used to target the models of solid tumors originated from human GBM CSC multicellular tumor spheroids (MCTS)...
March 20, 2018: Biomaterials Science
Hongyun Zhao, Meng Wu, Leilei Zhu, Yi Tian, Mingxing Wu, Yizhen Li, Liming Deng, Wei Jiang, Wei Shen, Zhigang Wang, Zhechuan Mei, Pan Li, Haitao Ran, Zhiyi Zhou, Jianli Ren
Objective: Prepare a multifunctional ultrasound molecular probe, hyaluronic acid-mediated cell-penetrating peptide-modified 10-hydroxycamptothecin-loaded phase-transformation lipid nanoparticles (HA/CPPs-10-HCPT-NPs), and to combine HA/CPPs-10-HCPT-NPs with low-intensity focused ultrasound (LIFU) for precision theranostics against hepatocellular carcinoma (HCC). Methods: HA/CPPs-10-HCPT-NPs were prepared using thin-film dispersion, ultrasound emulsification, and electrostatic effects. HA/CPPs-10-HCPT-NPs were characterized for particle size, zeta potential, encapsulation efficiency and drug-loading efficiency...
2018: Theranostics
Yunlei Zhang, Wei Ji, Lian He, Yiyan Chen, Xuezhi Ding, Yunjun Sun, Shengbiao Hu, Huijun Yang, Weitao Huang, Youming Zhang, Fei Liu, Liqiu Xia
Purpose: Systemic administration of free chemotherapeutic drugs leads to severe toxic effects, and physiological characteristics of solid tumors restrain the drugs from reaching the hypoxic regions. E. coli Nissle 1917 (EcN) has been known to penetrate the barrier and proliferate in the interface between the viable and necrotic regions of tumors. This study aimed to fabricate a nanoscale minicell via genetic engineering of EcN for targeted delivery of chemotherapeutic drugs to the hypoxic regions of tumors for cancer therapy...
2018: Theranostics
Genshen Zhong, Zhishan Xu, Ru Yang, Shenghua Zhang, Liang Li, Minna Wu, Hongtao Liu, Yongsu Zhen
Pancreatic cancer (PC) is one of the most dangerous cancers with less than 5% survival rate in 5 years. This study was to evaluate the antitumor activities of dFv-LDP-AE and dFv-R-LDP-AE, two energized fusion protein targeting gelatinases, on pancreatic cancer. The fusion protein dFv-LDP-AE consists of two tandem anti-gelatianses scFv and an enediyne antibiotic lidamycin (LDM) for receptor binding and cell killing. To improve the penetration capability, the fusion protein dFv-LDP-AE was integrated with an arginine-rich cell penetrating peptide (Arg)9 and then generated the fusion protein dFv-R-LDP-AE...
2018: Journal of Cancer
Hongchen Hua, Xuemei Zhang, Hongjie Mu, Qingqing Meng, Ying Jiang, Yiyun Wang, Xiaoyan Lu, Aiping Wang, Sha Liu, Yaping Zhang, Zhihui Wan, Kaoxiang Sun
Gliomas are the most common malignant brain tumor, but treatment is limited by the blood-brain barrier (BBB), especially for chemotherapeutic drugs. Although some chemotherapy drugs can pass through the BBB, many of these agents are toxic to normal brain tissue. To maximize therapeutic effects, chemotherapeutic drugs must accumulate at the glioma site. In this study, a specific ligand (the RVG29 peptide) that can combine with acetylcholine receptors was conjugated to polyethylene glycol-modified poly-(D,L-lactide-co-glycolide) (PEG-PLGA) to develop a targeted carrier; preparation of the targeted docetaxel nanoparticles (DTX-NPs) was performed by the nanoprecipitation method...
March 16, 2018: International Journal of Pharmaceutics
Anthony J Snyder, Pranav Danthi
Mammalian orthoreovirus (reovirus) utilizes pore forming peptides to penetrate host cell membranes. This step is essential for delivering its genome containing core particle during viral entry. This protocol describes an in vitro assay for measuring reovirus-induced pore formation.
January 20, 2018: Bio-protocol
Dirk van den Brand, Cornelia Veelken, Leon Massuger, Roland Brock
Drug delivery into tumors and metastases is a major challenge in the eradication of cancers such as epithelial ovarian carcinoma. Cationic cell-penetrating peptides (CPPs) are a promising group of delivery vehicles to mediate cellular entry of molecules that otherwise poorly enter cells. However, little is known about their penetration behavior in tissues. Here, we investigated penetration of cationic CPPs in 3D ovarian cancer spheroids and patient-derived 3D tumor explants. Penetration kinetics and distribution after long-term incubation were imaged by confocal microscopy...
March 14, 2018: Biochimica et Biophysica Acta
Chye Soi Moi, Chia Kin Yen, Khuen Yen Ng, Koh Rhun Yian
Protein misfolding and aggregation have been considered the common pathological hallmarks for a number of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD). These abnormal proteins aggregation damage mitochondria and induce oxidative stress and resulting neuronal cell death. Prolong neuronal damage activates microglia and astrocytes, development of inflammation reaction and further promotes neurodegeneration. Thus, elimination of abnormal proteins aggregation without eliciting any adverse effects are the main treatment strategies...
March 15, 2018: CNS & Neurological Disorders Drug Targets
Caroline K Søgaard, Siver A Moestue, Morten B Rye, Jana Kim, Anala Nepal, Nina-Beate Liabakk, Siri Bachke, Tone F Bathen, Marit Otterlei, Deborah K Hill
Docetaxel is the chemotherapeutic choice for metastatic hormone-refractory prostate cancer, however, it only marginally improves the survival rate. The purpose of the present study was to examine if a peptide targeting the cellular scaffold protein PCNA could improve docetaxel's efficacy. We found that docetaxel given in combination with a cell penetrating peptide containing the AlkB homolog 2 PCNA interacting motif (APIM-peptide), reduced the prostate volume and limited prostate cancer regrowth in vivo in the immunocompetent transgenic adenocarcinoma model of prostate cancer (TRAMP)...
February 20, 2018: Oncotarget
Emily Wonder, Lorena Simón-Gracia, Pablo Scodeller, Ramsey N Majzoub, Venkata Ramana Kotamraju, Kai K Ewert, Tambet Teesalu, Cyrus R Safinya
Cationic liposome-nucleic acid (CL-NA) complexes, which form spontaneously, are a highly modular gene delivery system. These complexes can be sterically stabilized via PEGylation [PEG: poly (ethylene glycol)] into nanoparticles (NPs) and targeted to specific tissues and cell types via the conjugation of an affinity ligand. However, there are currently no guidelines on how to effectively navigate the large space of compositional parameters that modulate the specific and nonspecific binding interactions of peptide-targeted NPs with cells...
March 2, 2018: Biomaterials
Xiubao Chang, Yuexian Hou
Genome editing is a powerful tool to modify a specific gene and to correct a disease-causing mutation. Recently developed new techniques, such as zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALEN) and clustered regularly interspaced short palindromic repeats/Cas9 (CRISPR/Cas9), significantly facilitate the progression in this field. However, mutations associated with the double strand DNA breaks (DSBs) introduced by these systems hampered their direct usage in clinic. In order to prevent the mutations caused by DSBs, we have designed a novel mean to induce homology-directed recombination (HDR) without DSBs, i...
2018: International Journal of Biochemistry and Molecular Biology
Shota Ichimizu, Hiroshi Watanabe, Hitoshi Maeda, Keisuke Hamasaki, Yuka Nakamura, Victor Tuan Giam Chuang, Ryo Kinoshita, Kento Nishida, Ryota Tanaka, Yuki Enoki, Yu Ishima, Akihiko Kuniyasu, Yoshihiro Kobashigawa, Hiroshi Morioka, Shiro Futaki, Masaki Otagiri, Toru Maruyama
Human serum albumin (HSA) is a superior carrier for delivering extracellular drugs. However, the development of a cell-penetrating HSA remains a great challenge due to its low membrane permeability. We report herein on the design of a series of palmitoyl-poly-arginine peptides (CPPs) and an evaluation of their cell-penetrating effects after forming a complex with HSA for use in intracellular drug delivery. The palmitoyl CPPs forms a stable complex with HSA by anchoring itself to the high affinity palmitate binding sites of HSA...
March 9, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Katia Pane, Mariavittoria Verrillo, Angela Avitabile, Elio Pizzo, Mario Varcamonti, Anna Zanfardino, Antimo Di Maro, Camilla Rega, Angela Amoresano, Viviana Izzo, Alberto Di Donato, Valeria Cafaro, Eugenio Notomista
Peptides with an N-terminal cysteine residue allow site-specific modification of proteins and peptides and chemical synthesis of proteins. They have been widely used to develop new strategies for imaging, drug discovery, diagnostics and chip technologies. Here we present a method to produce recombinant peptides with an N-terminal cysteine residue as a convenient alternative to chemical synthesis. The method is based on the release of the desired peptide from a recombinant fusion protein by mild acid hydrolysis of an Asp-Cys sequence...
March 12, 2018: Bioconjugate Chemistry
Rui Huang, Jiawei Li, Dereje Kebebe, Yumei Wu, Bing Zhang, Zhidong Liu
Tumor-targeted delivery is considered a crucial component of current anticancer drug development and is the best approach to increase the efficacy and reduce the toxicity. Nanomedicine, particularly ligand-based nanoparticles have shown a great potential for active targeting of tumor. Cell penetrating peptide is one of the promising ligands in a targeted cancer therapy. In this study, the gambogic acid-loaded nanostructured lipid carrier (GA-NLC) was modified with two kinds of cell penetrating peptides (cRGD and RGERPPR)...
November 2018: Drug Delivery
Md Zahidul Islam, Sabrina Sharmin, Md Moniruzzaman, Masahito Yamazaki
Cell-penetrating peptides (CPPs) can translocate across the plasma membrane of living eukaryotic cells and enter the cytosol without significantly affecting cell viability. Consequently, CPPs have been used for the intracellular delivery of biological cargo such as proteins and oligonucleotides. However, the mechanisms underlying the translocation of CPPs across the plasma membrane remain unclear. In this mini-review, we summarize the experimental results regarding the entry of CPPs into lipid bilayer vesicles obtained using three methods: the large unilamellar vesicle (LUV) suspension method, the giant unilamellar vesicle (GUV) suspension method, and the single GUV method...
March 9, 2018: Applied Microbiology and Biotechnology
Alphonse Garcia
Small viral proteins with cationic domains can be involved in multiple biological processes including cell penetration or interaction with intracellular targets. Within the last two decades several reports indicated that the C-terminus of HIV-1 Vpr is a cell penetrating sequence, a PP2A-dependent death domain and also displays toxicity against Gram-negative E. coli. Interestingly, HIV-1 Vpr, as well as some cationic proteins encoded by different viruses, share similar physical properties with the unique anti-microbial human cathelicidin LL37 peptide...
April 2018: Medical Hypotheses
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