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Cell penetrating peptides

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https://www.readbyqxmd.com/read/28938600/application-of-dual-targeting-drug-delivery-system-for-the-improvement-of-anti-glioma-efficacy-of-doxorubicin
#1
Zhenliang Sun, Xuebing Yan, YiBo Liu, Linsheng Huang, Cheng Kong, Xiao Qu, Man Wang, Renyuan Gao, Huanlong Qin
Chemotherapy of glioma is always hampered by the unsatisfactory tumor accumulation of drugs, of which the most noticeable obstacle is the limited drug permeability from vessels into tumor inner. In the present study, we developed a novel nanocarrier for the delivery of doxorubicin to brain tumor. Such novel drug delivery system was mainly composed of a tumor homing peptide and DOX-loaded PLA nanoparticles (AP1-NP-DOX). CRKRLDRNC peptide, named as AP1, was a newly glioma affinity peptide which could specifically binds to interleukin-4 receptor (IL-4R), highly expressing on both glioma cells and angiogenesis...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28937732/reducing-agent-assisted-excessive-galvanic-replacement-mediated-seed-mediated-synthesis-of-porous-gold-nanoplates-and-highly-efficient-gene-thermo-cancer-therapy
#2
Seounghun Kang, Kyunglee Kang, Hyun Huh, Hyungjun Kim, Sung-Jin Chang, Tae Jung Park, Ki Soo Chang, Dal-Hee Min, Hongje Jang
Porous Au nanoplates (pAuNPs) were manufactured by a reducing agent-assisted galvanic replacement reaction on Ag nanoplates using a seed-mediated synthetic approach. Two core additives, polyvinylpyrrolidone and L-ascorbic acid, prevented fragmentation and proceeded secondary growth. By controlling the concentration of the additives and the amount of replacing ion AuCl4-, various nanostructures including nanoplates with holes, nanoframes, porous nanoplates, and bumpy nanoparticles with unity and homogeneity were synthesized...
September 22, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28936509/x-ray-responsive-nanoparticles-with-triggered-release-of-nitrite-a-precursor-of-reactive-nitrogen-species-for-enhanced-cancer-radiosensitization
#3
Fang Liu, Junzhe Lou, Dimitre Hristov
Remotely and locally triggered release of therapeutic species by X-ray irradiation is highly desired to enhance the efficacy of radiotherapy. However, the development of such X-ray responsive nanosystems remains a challenge, especially in response to high energy clinically relevant X-ray radiation. Herein, we report novel nitroimidazole ligated gold nanoparticles (AuNPs) that synergistically function to release nitrite, an important precursor for nitric oxide and reactive nitrogen species that sensitize cancer cells, upon radiation with clinically used 6 MeV X-rays, while no release was detected without radiation...
September 22, 2017: Nanoscale
https://www.readbyqxmd.com/read/28935716/proteomic-analysis-of-phytophthora-infestans-reveals-the-importance-of-cell-wall-proteins-in-pathogenicity
#4
Svante Resjö, Maja Brus, Ashfaq Ali, Harold J G Meijer, Marianne Sandin, Francine Govers, Fredrik Levander, Laura Grenville-Briggs, Erik Andreasson
The oomycete Phytophthora infestans is the most harmful pathogen of potato. It causes the disease late blight, which generates increased yearly costs of up to one billion euro in the EU alone and is difficult to control. We have performed a large-scale quantitative proteomics study of six P. infestans life stages with the aim to identify proteins that change in abundance during development, with a focus on pre-infectious life stages. Over 10 000 peptides from 2061 proteins were analysed. We identified a number of abundance profiles of proteins that were up- or downregulated in different combinations of life stages...
September 21, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28935594/self-replicating-rna-vaccine-functionality-modulated-by-fine-tuning-of-polyplex-delivery-vehicle-structure
#5
Thomas Démoulins, Thomas Ebensen, Kai Schulze, Pavlos C Englezou, Panagiota Milona, Maria Pelliccia, Carlos A Guzmán, Nicolas Ruggli, Kenneth C McCullough
The major limitations with large and complex self-amplifying RNA vaccines (RepRNA) are RNase-sensitivity and inefficient translation in dendritic cells (DCs). Condensing RepRNA with polyethylenimine (PEI) gave positive in vitro readouts, but was largely inferior to virus-like replicon particles (VRP) or direct electroporation. In the present study, we improved such polyplex formulation and determined that fine-tuning of the polyplex structure is essential for ensuring efficacious translation. Thereby, three parameters dominate: (i) PEI molecular weight (MW); (ii) RepRNA:PEI (weight:weight) ratio; and (iii) inclusion of cell penetrating peptides (CPPs)...
September 18, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28933201/glioma-and-microenvironment-dual-targeted-nanocarrier-for-improved-antiglioblastoma-efficacy
#6
Xiuzhen Wang, Qing Zhang, Lingyan Lv, Junjie Fu, Yan Jiang, Hongliang Xin, Qizheng Yao
Drug delivery systems based on nanoparticles (nano-DDS) have aroused attentions for the treatment of glioblastoma (GBM), the most malignant brain cancer with a dismal prognosis. However, there are still numerous unmet challenges for traditional nano-DDS, such as the poor nanoparticle penetration, short retention in the GBM parenchyma and low glioma targeting ability. Herein, we used Pep-1 and CREKA peptides to construct a novel multifunctional GBM targeting nano-DDS (PC-NP). Pep-1 was used to overcome the blood-brain tumor barrier (BBTB) and home to glioma cells via interleukin-13 receptor-α2-mediated endocytosis, and CREKA was used to bind to fibrin-fibronectin complexes abundantly expressed in tumor microenvironment for enhanced retention in the GBM...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28933182/synthesis-and-cellular-characterization-of-various-nano-assemblies-of-cell-penetrating-peptide-epirubicin-polyglutamate-conjugates-for-the-enhancement-of-antitumor-activity
#7
Samaneh Mohammadi, Parvin Zakeri-Milani, Nasim Golkar, Samad Mussa Farkhani, Ali Shirani, Javid Shahbazi Mojarrad, Ali Nokhodchi, Hadi Valizadeh
A new class of cell penetrating peptides (CPPs) named peptide amphiphile was designed to improve the intracellular uptake and the antitumor activity of epirubicin (EPR). Various amphiphilic CPPs were synthesized by solid phase peptide synthesis method and were chemically conjugated to EPR. Their corresponding nanoparticles (CPPs-E4 and CPPs-E8) were prepared via non-covalent binding of the peptides and polyanions. Cytotoxicity and anti-proliferative activity were evaluated by MTT assay. Cellular uptake was examined by flow cytometry and fluorescence microscopy...
September 21, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28929019/heterologous-expression-of-plasmodium-vivax-apical-membrane-antigen-1-pvama1-for-binding-peptide-selection
#8
Ching Hoong Chew, Yvonne Ai Lian Lim, Kek Heng Chua
BACKGROUND: Plasmodium is an obligate intracellular parasite. Apical membrane antigen 1 (AMA1) is the most prominent and well characterized malarial surface antigen that is essential for parasite-host cell invasion, i.e., for sporozoite to invade and replicate within hepatocytes in the liver stage and merozoite to penetrate and replicate within erythrocytes in the blood stage. AMA1 has long served as a potent antimalarial drug target and is a pivotal vaccine candidate. A good understanding of the structure and molecular function of this Plasmodium protein, particularly its involvement in host-cell adhesion and invasion, is of great interest and hence it offers an attractive target for the development of novel therapeutics...
2017: PeerJ
https://www.readbyqxmd.com/read/28927928/discerning-the-composition-of-penetratin-for-safe-penetration-from-cornea-to-retina
#9
Kuan Jiang, Xin Gao, Qing Shen, Changyou Zhan, Yanyu Zhang, Cao Xie, Gang Wei, Weiyue Lu
Delivery of biomacromolecules into the eye is greatly hindered by several protective barriers. The cell-penetrating peptide, penetratin, has been found to be an effective absorption enhancer for noninvasive intraocular gene delivery. To discern the composition of penetratin for safe penetration from cornea to retina, we designed a series of penetratin derivatives by varying the hydrophobicity and evaluated their potency for retina-targeted delivery. The hydrophilic amino acids of penetratin, excluding the conserved basic amino acid residues, were respectively replaced with tryptophan...
September 18, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28921993/lactam-stapled-cell-penetrating-peptides-cell-uptake-and-membrane-binding-properties
#10
Marco J Klein, Samuel Schmidt, Parvesh Wadhwani, Jochen Bürck, Johannes Reichert, Sergii Afonin, Marina Berditsch, Tim Schober, Roland Brock, Manfred Kansy, Anne S Ulrich
Stapling of side chains to stabilize an α-helical structure has been generally associated with an increased uptake of CPPs. Here, we compare 4 amphiphilic stapled peptides with their linear counterparts in terms of their membrane binding and conformational features, in order to correlate these with uptake efficiency and toxicological effects. The impact of lactam stapling was found to vary strongly with regard to the different aspects of peptide-membrane interactions. Nearly all stapled peptides caused less membrane perturbation (vesicle leakage, hemolysis, bacterial lysis) than their linear counterparts...
September 18, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28921048/antibacterial-and-antitumor-activity-of-bogorol-b-jx-isolated-from-brevibacillus-laterosporus-jx-5
#11
Hongxia Jiang, Chao Ji, Junkang Sui, Rongbo Sa, Xiaohui Wang, Xunli Liu, Tai L Guo
Antimicrobial peptides are promising anti-infective agent candidates because they have a broad antimicrobial spectrum and bioactivity and are unlikely to elicit antibiotic resistance. The bogorols represent a new cationic antibiotic peptide and possess great therapeutic potential because of their bioactivity and precise mode of action. Here, we report that Bogorol B-JX (BBJX), a peptide previously isolated from Brevibacillus laterosporus JX-5 by us, has significant antibacterial and antitumor activities in vitro...
September 18, 2017: World Journal of Microbiology & Biotechnology
https://www.readbyqxmd.com/read/28919344/fluorophore-labeling-of-a-cell-penetrating-peptide-induces-differential-effects-on-its-cellular-distribution-and-affects-cell-viability
#12
Ditlev Birch, Malene Vinther Christensen, Dan Staerk, Henrik Franzyk, Hanne Mørck Nielsen
Cell-penetrating peptides constitute efficient delivery vectors, and studies of their uptake and mechanism of translocation typically involve fluorophore-labeled conjugates. In the present study, the influence of a number of specific fluorophores on the physico-chemical properties and uptake-related characteristics of penetratin were studied. An array of seven fluorophores belonging to distinct structural classes was examined, and the impact of fluorophore labeling on intracellular distribution and cytotoxicity was correlated to the physico-chemical properties of the conjugates...
September 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28918028/human-dmbt1-derived-cell-penetrating-peptides-for-intracellular-sirna-delivery
#13
Martina Tuttolomondo, Cinzia Casella, Pernille Lund Hansen, Ester Polo, Luciana M Herda, Kenneth A Dawson, Henrik J Ditzel, Jan Mollenhauer
Small interfering RNA (siRNA) is a promising molecule for gene therapy, but its therapeutic administration remains problematic. Among the recently proposed vectors, cell-penetrating peptides show great promise in in vivo trials for siRNA delivery. Human protein DMBT1 (deleted in malignant brain tumor 1) is a pattern recognition molecule that interacts with polyanions and recognizes and aggregates bacteria. Taking advantage of these properties, we investigated whether specific synthetic DMBT1-derived peptides could be used to formulate nanoparticles for siRNA administration...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28917447/cell-penetrating-peptides-to-dissect-host-pathogen-protein-protein-interactions-in-theileria-transformed-leukocytes
#14
REVIEW
Malak Haidar, Perle Latré de Laté, Eileen J Kennedy, Gordon Langsley
One powerful application of cell penetrating peptides is the delivery into cells of molecules that function as specific competitors or inhibitors of protein-protein interactions. Ablating defined protein-protein interactions is a refined way to explore their contribution to a particular cellular phenotype in a given disease context. Cell-penetrating peptides can be synthetically constrained through various chemical modifications that stabilize a given structural fold with the potential to improve competitive binding to specific targets...
September 7, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28912890/glioma-dual-targeting-nanohybrid-protein-toxin-constructed-by-intein-mediated-site-specific-ligation-for-multistage-booster-delivery
#15
Yingzhi Chen, Meng Zhang, Hongyue Jin, Dongdong Li, Fan Xu, Aihua Wu, Jinyu Wang, Yongzhuo Huang
Malignant glioma is one of the most untreatable cancers because of the formidable blood-brain barrier (BBB), through which few therapeutics can penetrate and reach the tumors. Biologics have been booming in cancer therapy in the past two decades, but their application in brain tumor has long been ignored due to the impermeable nature of BBB against effective delivery of biologics. Indeed, it is a long unsolved problem for brain delivery of macromolecular drugs, which becomes the Holy Grail in medical and pharmaceutical sciences...
2017: Theranostics
https://www.readbyqxmd.com/read/28910080/cell-surface-interactions-on-arginine-rich-cell-penetrating-peptides-allow-for-multiplex-modes-of-internalization
#16
Shiroh Futaki, Ikuhiko Nakase
One of the recent hot topics in peptide-related chemical biology research is the potential of cell-penetrating peptides (CPPs). Owing to their ability to deliver exogenous molecules into cells easily and effectively, their flexible design that allows transporters to comprise various chemical structures and functions, and their potential in chemical and cell biology studies and clinical applications, CPPs have been attracting enormous interest among researchers in related fields. Consequently, publications on CPPs have increased significantly...
September 14, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28901372/multivalent-gold-nanoparticle-peptide-conjugates-for-targeting-intracellular-bacterial-infections
#17
Rimi Chowdhury, Humaira Ilyas, Anirban Ghosh, Haydar Ali, Arup Ghorai, Anupam Midya, Nikhil R Jana, Santasabuj Das, Anirban Bhunia
Although nanoparticle-tagged antimicrobal peptides have gained considerable importance in recent years, their structure-function correlation has not yet been explored. Here, we have studied the mechanism of action of a designed antimicrobial peptide, VG16KRKP (VARGWKRKCPLFGKGG), delivered via gold nanoparticle tagging against Salmonella infection by combining biological experiments with high- and low-resolution spectroscopic techniques. In comparison with the free VG16KRKP peptide or gold nanoparticle alone, the conjugated variant, Au-VG16KRKP, is non-cytotoxic to eukaryotic cells, but exhibits strong bacteriolytic activity in culture...
September 13, 2017: Nanoscale
https://www.readbyqxmd.com/read/28895366/-purification-identification-and-characterization-of-an-anti-microbial-hexapeptide-from-sus-scrofa-lysozyme
#18
Dewei Zhu, Guolin Cai, Jian Lu
Sus scrofa lysozyme (SSL) was digested by different proteases to find peptides with enhanced antibacterial activity against gram-negative bacteria. Hydrolysate with the highest anti-bacterial activity was loaded onto a gel filtration chromatography column followed by a reversed-phase one. The obtained substance was identified by liquid chromatography-mass spectrometry, synthesized to test its antibacterial spectrum and analyzed for bioinformatics. The hydrolysate of trypsin showed the highest antibacterial activity...
June 25, 2017: Sheng Wu Gong Cheng Xue Bao, Chinese Journal of Biotechnology
https://www.readbyqxmd.com/read/28888370/biophysical-and-biological-properties-of-small-linear-peptides-derived-from-crotamine-a-cationic-antimicrobial-antitumoral-toxin-with-cell-penetrating-and-cargo-delivery-abilities
#19
C Dal Mas, D A Pinheiro, J D Campeiro, B Mattei, V Oliveira, E B Oliveira, A Miranda, K R Perez, M A F Hayashi
Crotamine is a natural polypeptide from snake venom which delivers nucleic acid molecules into cells, besides having pronounced affinity for negatively charged membranes and antifungal activity. We previously demonstrated that crotamine derived short linear peptides were not very effective as antifungal, although the non-structured recombinant crotamine was overridingly more potent compared to the native structured crotamine. Aiming to identify the features necessary for the antifungal activity of crotamine, two linear short peptides, each comprising half of the total positively charged amino acid residues of the full-length crotamine were evaluated here to show that these linear peptides keep the ability to interact with lipid membrane model systems with different phospholipid compositions, even after forming complexes with DNA...
September 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28887220/enhanced-glioma-therapy-by-synergistic-inhibition-of-autophagy-and-tyrosine-kinase-activity
#20
Xuhui Wang, Yue Qiu, Qianwen Yu, Hui Li, Xiaoxiao Chen, Man Li, Yang Long, Yayuan Liu, Libao Lu, Jiajing Tang, Zhirong Zhang, Qin He
Autophagy is a lysosomal degradation pathway that acts as a cytoprotective mechanism causing treatment resistance in various cancer cells. Recent studies showed that hydroxychloroquine can inhibit the latter step of autophagy and therefore enhance the anti-glioma efficiency of ZD6474, a tyrosine kinase inhibitor. However, the nonselective distribution of ZD6474 in vivo and the low penetrating ability of hydroxychloroquine when crossing the blood-brain barrier restrict their clinical use in glioma therapy. Here we coencapsulated ZD6474 and hydroxychloroquine into R6dGR peptide-modified liposomes (R6dGR-Lip) which can specifically recognize both integrin αvβ3 and neuropilin-1 receptors that are highly expressed on the endothelial cells and glioma cells...
September 5, 2017: International Journal of Pharmaceutics
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