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Cell penetrating peptides

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https://www.readbyqxmd.com/read/28727430/renal-clearable-peptide-functionalized-nagdf4-nanodots-for-high-efficiency-tracking-orthotopic-colorectal-tumor-in-mouse
#1
Hongda Chen, Xiaodong Li, Fuyao Liu, Huimao Zhang, Zhenxin Wang
The effective delivery of bioimaging probes to a selected cancerous tissue has extensive significance for biological studies and clinical investigations. Herein, the peptide functionalized NaGdF4 nanodots (termed as, pPeptide-NaGdF4 nanodots) have been prepared for highly efficient magnetic resonance imaging (MRI) of tumor by formation of Gd-phosphonate coordinate bonds among hydrophobic NaGdF4 nanodots (4.2 nm in diameter) with mixed phosphorylated peptide ligands including a tumor targeting phosphopeptide and a cell penetrating phosphopeptide...
July 20, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28718401/targeting-atf5-in-cancer
#2
James M Angelastro
The expression of activating transcription factor 5 (ATF5) correlates negatively with patient survival in different types of cancer. ATF5 is important for the survival and proliferation of cancer cells, and can be targeted to selectively trigger cancer cell apoptosis while sparing normal cells. Cell-penetrating peptides combined with a dominant negative ATF5 cargo have recently shown efficacy against brain, breast, melanoma, and prostate cancers.
July 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28716758/oral-delivery-of-vancomycin-by-tetraether-lipid-liposomes
#3
Philipp Uhl, Silvia Pantze, Philip Storck, Johannes Parmentier, Dominik Witzigmann, Götz Hofhaus, Jörg Huwyler, Walter Mier, Gert Fricker
Despite the outstanding progress in modern medicine, the oral delivery of peptide drugs is limited until today due to their instability in the gastrointestinal tract and low mucosa penetration. To overcome these hurdles, liposomes containing the specific tetraether lipid GCTE (glycerylcaldityltetraether lipid) were examined. For this purpose, the glycopeptide antibiotic vancomycin was used as model substance and liposomes were prepared by DAC (dual assymetric centrifugation). These liposomes showed a size and polydispersity index comparable to standard liposomes...
July 14, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28715655/macrophage-exosomes-as-natural-nanocarriers-for-protein-delivery-to-inflamed-brain
#4
Dongfen Yuan, Yuling Zhao, William A Banks, Kristin M Bullock, Matthew Haney, Elena Batrakova, Alexander V Kabanov
Recent work has stimulated interest in the use of exosomes as nanocarriers for delivery of small drugs, RNAs, and proteins to the central nervous system (CNS). To overcome the blood-brain barrier (BBB), exosomes were modified with brain homing peptides that target brain endothelium but likely to increase immune response. Here for the first time we demonstrate that there is no need for such modification to penetrate the BBB in mammals. The naïve macrophage (Mϕ) exosomes can utilize, 1) on the one hand, the integrin lymphocyte function-associated antigen 1 (LFA-1) and intercellular adhesion molecule 1 (ICAM-1), and, 2) on the other hand, the carbohydrate-binding C-type lectin receptors, to interact with brain microvessel endothelial cells comprising the BBB...
July 10, 2017: Biomaterials
https://www.readbyqxmd.com/read/28715199/jumping-hurdles-peptides-able-to-overcome-biological-barriers
#5
Macarena Sánchez-Navarro, Meritxell Teixidó, Ernest Giralt
The cell membrane, the gastrointestinal tract, and the blood-brain barrier (BBB) are good examples of biological barriers that define and protect cells and organs. They impose different levels of restriction, but they also share common features. For instance, they all display a high lipophilic character. For this reason, hydrophilic compounds, like peptides, proteins, or nucleic acids have long been considered as unable to bypass them. However, the discovery of cell-penetrating peptides (CPPs) opened a vast field of research...
July 17, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28712848/a-short-region-of-connexin43-reduces-human-glioma-stem-cell-migration-invasion-and-survival-through-src-pten-and-fak
#6
Myriam Jaraíz-Rodríguez, Ma Dolores Tabernero, María González-Tablas, Alvaro Otero, Alberto Orfao, Jose M Medina, Arantxa Tabernero
Connexin43 (CX43), a protein that forms gap junction channels and hemichannels in astrocytes, is downregulated in high-grade gliomas. Its relevance for glioma therapy has been thoroughly explored; however, its positive effects on proliferation are counterbalanced by its effects on migration and invasion. Here, we show that a cell-penetrating peptide based on CX43 (TAT-Cx43266-283) inhibited c-Src and focal adhesion kinase (FAK) and upregulated phosphatase and tensin homolog in glioma stem cells (GSCs) derived from patients...
July 3, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28705677/hyicin-4244-the-first-sactibiotic-described-in-staphylococci-exhibits-an-anti-staphylococcal-biofilm-activity
#7
Andreza Freitas de Souza Duarte, Hilana Ceotto-Vigoder, Emile Santos Barrias, Thaïs Cristina Baeta Soares Souto-Padrón, Ingolf Figved Nes, Maria do Carmo de Freire Bastos
Hyicin 4244 is a small antimicrobial peptide with a broad-spectrum of activity found in the culture supernatant of Staphylococcus hyicus 4244, whose genome was then sequenced. The bacteriocin gene cluster (hyiSABCDEFG) was mined from its single chromosome and exhibited a genetic organization similar to that of subtilosin A. All genes involved in hyicin 4244 biosynthesis proved to be transcribed and encode proteins that share at least 42 % similarity to proteins encoded by the subtilosin A gene cluster. Due to its resemblance to subtilosin A and the presence of three thioether bonds in its structure, hyicin 4244 is assumed to be a 35 amino acid circular sactibiotic, the first to be described in staphylococci...
July 10, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28704609/hydrophilic-and-cell-penetrable-pyrrolidinyl-peptide-nucleic-acid-pna-via-post-synthetic-modification-with-hydrophilic-side-chains
#8
Chaturong Suparpprom, Thanesuan Nuanyai, Haruthai Pansuwan, Tirayut Vilaivan, Supason Wanichwecharungruang, Boonsong Ditmangklo, Tanapat Palaga, Porntip Pan-In, Banphot Jiangchareon, Chotima Vilaivan
Peptide Nucleic Acid (PNA) is a nucleic acid mimic in which the deoxyribose-phosphate was replaced by a peptide-like backbone. The absence of negative charge in the PNA backbone leads to several unique behaviors including a stronger binding and salt-independency of the PNA-DNA duplex stability. However, PNA possesses poor aqueous solubility and cannot directly penetrate cell membranes. These are major obstacles that limited in vivo applications of PNA. In previous strategies, the PNA can be conjugated to macromolecular carrier, or modified with positively charged side chains such as guanidinium groups to improve the aqueous solubility and/or cell permeability...
July 13, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28700237/rgd-modified-albumin-nanoconjugates-for-targeted-delivery-of-a-porphyrin-photosensitizer
#9
Fang Li, Yan Zhao, Chengqiong Mao, Yi Kong, Xin Ming
Advances in photodynamic therapy of cancer have been restrained by lack of cancer specificity and side effects to normal tissues. Molecularly targeted photodynamic therapy can achieve higher cancer specificity by combination of active cancer targeting and localized laser activation. We aimed to use albumin as a carrier to prepare targeted nanoconjugates that are selective to cancer cells and smaller than conventional nanoparticles for superior tumor penetration. IRDye® 700DX (IR700), a porphyrin photosensitizer, was covalently conjugated to human serum albumin that was also linked with tumor-targeting RGD peptides...
July 12, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28699828/glioma-targeted-delivery-strategy-of-doxorubicin-loaded-liposomes-by-dual-ligand-modification
#10
Wei Han, Guangfu Yin, Ximing Pu, Xianchun Chen, Xiaoming Liao, Zhongbing Huang
The blood-brain barrier (BBB) is the protective parclose of brain safety, but it is also the main obstacle of the drug delivery to cerebral parenchyma, which hamper therapy for brain diseases. In this work, a glioma targeted drug delivery system was developed through loading doxorubicin into Angiopep-2 and TAT peptide dual-modified liposomes (DOX-TAT-Ang-LIP). Low-density lipoprotein receptor-related protein-1 (LRP1) was one receptor overexpressed on both BBB and glioma cytomembranes. Angiopep-2, a specific ligand of LRP1, exhibited high LRP1 binding efficiency...
July 12, 2017: Journal of Biomaterials Science. Polymer Edition
https://www.readbyqxmd.com/read/28699537/recent-advances-in-polymeric-nanosystems-for-treating-cutaneous-melanoma-and-its-metastasis
#11
Yi-Ping Chou, Yin-Ku Lin, Chun-Han Chen, Jia-You Fang
Melanoma shows a high possibility of mortality after it metastasizes because of its aggressive nature. Although there are several options for anti-melanoma therapy, this skin malignancy is resistant to some therapies. Chemotherapy, biochemotherapy, immunotherapy, and adoptive cell therapy have failed to exhibit a significant amelioration in overall survival. Nanomedicine provides an opportunity to improve the efficiency of the anti-melanoma regimen. Nanoparticles for treating melanoma provide the advantages over conventional therapies such as drug solubility increment, drug stability enhancement, epithelium permeability and bioavailability amelioration, half-life prolonging, tumor targeting, and side effect minimization...
July 10, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28699510/cell-penetrating-peptides-a-promising-tool-for-the-cellular-uptake-of-macromolecular-drugs
#12
Peipei Zhu, Lan Jin
The lipid bilayer of the plasma membrane is a selective impermeable barrier for the internalization of most macromolecules. Cell penetrating peptides (CPPs) could cross the plasma membrane barrier to deliver various molecules into cells and are considered as a promising tool to deliver macromolecular drugs. However, the exact cellular uptake mechanisms of CPPs are still ambiguous. It was reported that the exact cellular uptake pathway was determined by numerous factors such as the amino acid sequences (hydrophobicity and net charge), extracellular CPP concentration, cargoes' properties, cell type and the temperature...
July 10, 2017: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/28699134/intraoperative-tumor-detection-using-a-ratiometric-activatable-fluorescent-peptide-a-first-in-human-phase-1-study
#13
Jonathan T Unkart, Steven L Chen, Irene L Wapnir, Jesús E González, Alec Harootunian, Anne M Wallace
BACKGROUND: Positive surgical margins remain a significant challenge in breast cancer surgery. This report describes the use of a novel, first-in-human ratiometric activatable cell-penetrating peptide in breast cancer surgery. METHODS: A two-part, multi-institutional phase 1 trial of AVB-620 with a 3+3 dose escalation and dose-expansion cohorts was conducted. The patients received an infusion of AVB-620 2-20 h before planned lumpectomy/mastectomy and sentinel node biopsy/axillary dissection...
July 11, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28694765/cellular-uptake-and-anti-tumor-activity-of-gemcitabine-conjugated-with-new-amphiphilic-cell-penetrating-peptides
#14
Parvin Zakeri-Milani, Samad Mussa Farkhani, Ali Shirani, Samaneh Mohammadi, Javid Shahbazi Mojarrad, Jafar Akbari, Hadi Valizadeh
Gemcitabine (Gem) is used as a single agent or in combination with other anticancer agents to treat many types of solid tumors. However, it has many limitations such as a short plasma half-life, dose-limiting toxicities and drug resistance. Cell-penetrating peptides (CPPs) are short peptides which may deliver a large variety of cargo molecules into the cancerous cells. The current study was designed to evaluate the antiproliferative activity of gemcitabine chemically conjugated to CPPs. The peptides were synthesized using solid phase synthesis procedure...
2017: EXCLI journal
https://www.readbyqxmd.com/read/28693996/human-epidermal-growth-factor-coupled-to-different-structural-classes-of-cell-penetrating-peptides-a-comparative-study
#15
Jing Chen, Haibin Li, Jianhua Chen
Human epidermal growth factor (hEGF) plays important roles in wound healing. Due to large molecular weight and hydrophilic nature, cellular uptake and skin permeation of hEGF are very poor, significantly limiting its efficacy. By using recombinant technology, four structural classes of cell penetrating peptides (CPPs) were fused at the C-terminus of hEGF, expressed and purified into homogeneity. Comparative studies were conducted to evaluate their activity, cytotoxicity, cellular uptake and skin permeation...
July 7, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28689990/graphene-oxide-nanosheets-in-complex-with-cell-penetrating-peptides-for-oligonucleotides-delivery
#16
Moataz Dowaidar, Hani Nasser Abdelhamid, Mattias Hällbrink, Xiaodong Zou, Ülo Langel
A new strategy for gene transfection using the nanocarrier of cell penetrating peptides (CPPs; PepFect14 (PF14) or PepFect14 (PF14) (PF221)) in complex with graphene oxide (GO) is reported. GO complexed with CPPs and plasmid (pGL3), splice correction oligonucleotides (SCO) or small interfering RNA (siRNA) are performed. Data show adsorption of CPPs and oligonucleotides on the top of the graphenic lamellar without any observed change of the particle size of GO. GO mitigates the cytotoxicity of CPPs and improves the material biocompatibility...
July 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28688684/early-detection-of-squamous-cell-carcinoma-in-carcinogen-induced-oral-cancer-rodent-model-by-ratiometric-activatable-cell-penetrating-peptides
#17
Dina V Hingorani, Aaron J Lemieux, Joseph R Acevedo, Heather L Glasgow, Suraj Kedarisetty, Michael A Whitney, Alfredo A Molinolo, Roger Y Tsien, Quyen T Nguyen
OBJECTIVES: Ratiometric cell-penetrating-peptides (RACPP) are hairpin-shaped molecules that undergo cleavage by tumor-associated proteases resulting in measurable Cy5:Cy7 fluorescence ratiometric change to label cancer in vivo. We evaluated an MMP cleavable RACPP for use in the early detection of malignant lesions in a carcinogen-induced rodent tumor model. METHODS: Wild-type immune-competent mice were given 4-nitroquinoline-oxide (4NQO) for 16weeks. Oral cavities from live mice that had been intravenously administered MMP cleavable PLGC(Me)AG-RACPP were serially imaged from week 11 through week 21 using white-light reflectance and Cy5:Cy7 ratiometric fluorescence...
August 2017: Oral Oncology
https://www.readbyqxmd.com/read/28686414/stimuli-responsive-cluster-bomb-for-programmed-tumor-therapy
#18
Qi Lei, Shi-Bo Wang, Jing-Jing Hu, Yi-Xiong Lin, Cheng-Hui Zhu, Lei Rong, Xian-Zheng Zhang
In this paper, mesoporous silica nanoparticle (MSN) loaded with doxorubicin (DOX) and capped with tumor homing/penetrating peptide tLyP-1-modified tungsten disulfide quantum dots (WS2-HP) was designed and applied as a stimuli-responsive "Cluster Bomb" for high-performance tumor suppression. The peptide tLyP-1 on the surface can both facilitate the homing of DOX@MSN-WS2-HP to 4T1 tumor and greatly enhance the penetration of WS2-HP in tumor. The benzoic-imine bonds as the linkers between "bomblets" and "dispenser" are stable under normal physical conditions and quite labile at pH 6...
July 7, 2017: ACS Nano
https://www.readbyqxmd.com/read/28685576/egfr-egfrviii-dual-targeting-peptide-mediated-drug-delivery-for-enhanced-glioma-therapy
#19
Jiani Mao, Danni Ran, Cao Xie, Qing Shen, Songli Wang, Weiyue Lu
Tumor-homing peptides have been widely used to mediate active targeted drug delivery. l-AE is a reported targeting peptide demonstrating high binding affinity to epidermal growth factor receptor (EGFR) and mutation variant III (EGFRvIII) overexpressed on neovasculature, vasculogenic mimicry, tumor cells, and tumor stem cells. To improve its proteolytic stability, a d-peptide ligand (termed d-AE, the enantiomer of l-AE) was developed. d-AE was confirmed to bind receptors EGFR and EGFRvIII with targeting capability comparable to l-AE...
July 17, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28682598/multistage-passive-and-active-delivery-of-radiolabeled-nanogels-for-superior-tumor-penetration-efficiency
#20
Natascha Drude, Smriti Singh, Oliver Horst Winz, Martin Moeller, Felix Manuel Mottaghy, Agnieszka Morgenroth
Development of nanosized drug delivery systems in cancer therapy is directed towards improving tumor selectivity and minimizing damages of healthy tissue. We introduce a delivery system with synergistic optimization and combination of passive and active targeting strategies. The approach is based on radiopeptide labeled redox sensitive hydrophilic nanogels, which exploit passive targeting by the enhanced permeability and retention effect while avoiding elimination by the mononuclear phagocyte system and fast hepatic and/or renal clearance...
July 6, 2017: Biomacromolecules
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