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Cell-penetrating peptides

Ikramy A Khalil, Seigo Kimura, Yusuke Sato, Hideyoshi Harashima
We report on the development of a highly efficient gene delivery system based on synergism between octaarginine (R8), a representative cell penetrating peptide, and YSK05, a recently developed pH-sensitive cationic lipid. Attaching a high density of R8 on the surface of YSK05 nanoparticles (NPs) that contained encapsulated plasmid DNA resulted in the formation of positively charged NPs with improved transfection efficiency. To avoid the development of a net positive charge, we controlled the density and topology of the R8 peptide through the use of a two-step coating methodology, in which the inner lipid coat was modified with a low density of R8 which was then covered with an outer neutral YSK05 lipid layer...
February 13, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Sang Won Choi, Rudra Pangeni, Dai Hyun Jung, Su Jung Kim, Jin Woo Park
The exogenous administration of growth factors has been examined for treating wounds and such factors serve as cosmetic agents for skin regeneration. However, the topical application of growth factors is hampered by their limited percutaneous absorption. In this study, we genetically modified basic fibroblast growth factor (bFGF) and vascular endothelial growth factor-A (VEGF-A) using a cell-penetrating peptide to facilitate their permeation into skin and to avoid multiple steps in the chemical or physical modification of biomaterials...
February 1, 2018: Journal of Nanoscience and Nanotechnology
Ching-Wei Tsai, Ze-Wei Lin, Wen-Fang Chang, Yi-Fan Chen, Wei-Wen Hu
Indolicidin (IL) is a cationic antimicrobial peptide and our previous study has demonstrated its potential as a cell penetrating peptide (CPP) to promote gene delivery. However, the cytotoxicity of IL arisen from its membrane perturbation capacity may restrict its clinical application. To promote gene delivery safety and efficiency, an almost mirror-symmetric IL derivative, SAP10 (RRWKFFPWRR-CONH 2 ), was designed in this study. All-atom molecular dynamics (MD) simulations were performed to understand the association between SAP10 and model lipid bilayers...
February 5, 2018: Colloids and Surfaces. B, Biointerfaces
Keith H Parsons, Mosharrof H Mondal, Charles L McCormick, Alex S Flynt
RNAi-based technologies are ideal for pest control as they can provide species specificity and spare non-target organisms. However, in some pests biological barriers prevent use of RNAi, and therefore broad application. In this study we tested the ability of a synthetic cationic polymer, poly-[N-(3-guanidinopropyl)methacrylamide] (pGPMA), that mimics arginine-rich cell penetrating peptides to trigger RNAi in an insensitive animal-Spodoptera frugiperda. Polymer-dsRNA interpolyelectrolyte complexes (IPECs) were found to be efficiently taken up by cells, and to drive highly efficient gene knockdown...
February 15, 2018: Biomacromolecules
Gaowei Hu, Wenlv Zheng, Ao Li, Yaru Mu, Mingyu Shi, Tuofan Li, Haitao Zou, Hongxia Shao, Aijian Qin, Jianqiang Ye
Cell-penetrating peptide (CPP) is a promising cargo for delivering bioactive molecules. In this study, the N terminus of VP1 from chicken anemia virus, designated as CVP1, was found to carry enriched arginine residues with α-helix. By confocal imaging, flow cytometry and MTT assay, we identified CVP1 as a novel, safe and efficient CPP. CVP1-FITC peptide could entry different types of cells tested with dose dependence, but without cytotoxic effects. Compared with TAT-FITC peptide, the CVP1-FITC peptide showed much higher cell-penetrating activity...
February 13, 2018: Veterinary Research
Blaine Jacobs, Miryam M Pando, Elaine M Jennings, Teresa S Chavera, William P Clarke, Kelly A Berg
There is abundant evidence for formation of G protein coupled receptor heteromers in heterologous expression systems, however, little is known of the function of heteromers in native systems. Heteromers of delta and kappa opioid receptors (DOR-KOR heteromers) have been identified in native systems. We previously reported that activation of DOR-KOR heteromers expressed by rat pain-sensing neurons (nociceptors) produces robust, peripherally-mediated antinociception. Moreover, DOR agonist potency and efficacy is regulated by KOR antagonists via allosteric interactions within the DOR-KOR heteromer in a ligand-dependent manner...
February 7, 2018: Molecular Pharmacology
Jie Ding, Tingxizi Liang, Qianhao Min, Li-Ping Jiang, Jun-Jie Zhu
For co-delivery of therapeutic genes and chemical agents in combined therapy, the ideal drug delivery system (DDS) entails high-capacity and low-body toxicity carriers, allowing adequate drug dose for tumor region while yielding low residue in normal tissue. To augment the gene/drug load capacity and circumvent the potential toxicity brought by traditional inorganic and polymeric nanocarriers, a "stealth" carrier was herein designed in a simple self-assembly of (-)-epigallocatechin-3-O-gallate (EGCG) and small interfering RNA (siRNA) by recruiting protamine as biodegradable medium for the treatment of drug-resistant triple-negative breast cancer (TNBC)...
February 13, 2018: ACS Applied Materials & Interfaces
Michal Feldman, Dan Levy
A large body of evidence accumulating in the past few years indicates the physiological significance of non-histone proteins lysine methylation, catalyzed by protein lysine methyl transferases (PKMTs). Dysregulation of these enzymes was shown to contribute to the development and progression of numerous diseases. SETD6 lysine methylatransferase was recently shown to participate in essential cellular processes, such as the NFkB pathway, oxidative stress and also the Wnt signaling cascade. In order to test the effect of blocking SETD6 catalytic activity, we used the peptide inhibition method, which is considered highly specific and can potentially target almost any protein...
January 12, 2018: Oncotarget
Song Qin, Zhipeng Gao, Yu Liu, Changbai Liu, Jun Wang, Li Li Zou
In cancer immunotherapy, dendritic cell (DC)-based vaccines represent a promising, yet challenging, treatment method. In addition to overcoming the low expression levels of antigenic epitopes on cancer cells, it is also necessary to overcome the inhibitory effect of suppressor of cytokine signaling 1 (SOCS1) on DC self-antigen presentation. Our group previously demonstrated that calreticulin (CRT) translocated type I transmembrane glycoprotein mucin 1 (MUC1), a breast cancer antigen, to the surface of 4T1 cells, and that treatment with MUC1-CRT-primed 4T1 cell-treated DCs induced apoptosis in a breast cancer cell line...
February 2018: Oncology Letters
Pranali Deshpande, Aditi Jhaveri, Bhushan Pattni, Swati Biswas, Vladimir Torchilin
Off-target effects of drugs severely limit cancer therapy. Targeted nanocarriers are promising to enhance the delivery of therapeutics to tumors. Among many approaches for active tumor-targeting, arginine-rich cell penetrating peptides (AR-CPP) and ligands specific to target over-expressed receptors on cancer-cell surfaces, are popular. Earlier, we showed that the attachment of an AR-CPP octaarginine (R8) to the surface of DOXIL® (Doxorubicin encapsulated PEGylated liposomes) improved cytoplasmic and nuclear DOX delivery that enhanced the cytotoxic effect in vitro and improved therapeutic efficacy in vivo...
November 2018: Drug Delivery
Md Mizanur Rahman Moghal, Md Zahidul Islam, Sabrina Sharmin, Victor Levadnyy, Md Moniruzzaman, Masahito Yamazaki
Entry of cell-penetrating peptides (CPPs) into living cells by translocating across plasma membranes is an important physiological phenomenon. To elucidate the mechanism of the translocation of CPPs across lipid bilayers, it is essential to reveal its elementary processes. For this purpose, here, we have developed a new method for the continuous, quantitative detection of the entry of CPPs into giant unilamellar vesicles (GUVs), where we investigate the interaction of fluorescent probe-labeled CPPs with single GUVs containing large unilamellar vesicles (LUVs) and fluorescent probes in their lumens using confocal microscopy...
February 6, 2018: Chemistry and Physics of Lipids
LeiLei Zhu, HongYun Zhao, ZhiYi Zhou, YongHong Xia, Zhigang Wang, Haitao Ran, Pan Li, JianLi Ren
In this study, we successfully developed a novel tumor homing-penetrating peptide - functionalized drug-loaded phase-transformation nanoparticles (tLyP-1-10-HCPT-PFP NPs) combining LIFU for tumor ultrasound molecular imaging and precise therapy. With the nanoscale particle size, tLyP-1-10-HCPT-PFP NPs could pass through the tumor vascular endothelial cell gap. Induced by tLyP-1 peptide with targeting and penetrating efficiency, tLyP-1-10-HCPT-PFP NPs could increase tumor accumulation and penetrate deeply into the extravascular tumor tissue, which penetrating through extracellular matrix, cellular membrane to cytoplasm even into cell nucleus...
February 8, 2018: Nano Letters
C Tudisco, M T Cambria, A E Giuffrida, F Sinatra, C D Anfuso, G Lupo, N Caporarello, A Falanga, S Galdiero, V Oliveri, C Satriano, G G Condorelli
A versatile synthetic route based on magnetic Fe3O4 nanoparticle (MNP) prefunctionalization with a phosphonic acid monolayer has been used to covalently bind the gH625 peptide on the nanoparticle surface. gH625 is a membranotropic peptide capable of easily crossing the membranes of various cells including the typical human blood-brain barrier components. A similar synthetic route was used to prepare another class of MNPs having a functional coating based on PEG, rhodamine, and folic acid, a well-known target molecule, to compare the performance of the two cell-penetrating systems (i...
February 7, 2018: Nanoscale Research Letters
Anqing Zhu, Huizi Sha, Shu Su, Fangjun Chen, Jia Wei, Fanyan Meng, Yang Yang, Juan Du, Jie Shao, Fuzhi Ji, Chong Zhou, Zhengyun Zou, Xiaoping Qian, Baorui Liu
Efficient trafficking of lymphocytes to the tumor microenvironment is crucial for the success of an effective antitumor immunotherapy. A major challenge to achieve effective adoptive immunotherapy is poor tumor penetration and inefficient migration of T cells to the tumor site. Several approaches to facilitate the trafficking of lymphocytes to the tumor microenvironment have been suggested to overcome these obstacles. Here, we address this issue with a focus on the tumor-penetrating peptide iRGD, which can specifically increase the permeability of the tumor vasculature and tumor tissue, enhancing drug penetration...
2018: American Journal of Cancer Research
Santiago Grijalvo, Adele Alagia, Andreia F Jorge, Ramon Eritja
Oligonucleotide-based therapy has become an alternative to classical approaches in the search of novel therapeutics involving gene-related diseases. Several mechanisms have been described in which demonstrate the pivotal role of oligonucleotide for modulating gene expression. Antisense oligonucleotides (ASOs) and more recently siRNAs and miRNAs have made important contributions either in reducing aberrant protein levels by sequence-specific targeting messenger RNAs (mRNAs) or restoring the anomalous levels of non-coding RNAs (ncRNAs) that are involved in a good number of diseases including cancer...
February 6, 2018: Genes
Sahrish Rehmani, James E Dixon
Oral delivery of insulin and other anti-diabetic peptides is inhibited by low intestinal absorption caused by the poor permeability across cellular membranes and the susceptibility to enzymatic degradation in the gastrointestinal tract. Cell-penetrating peptides (CPPs) have been investigated for a number of years as oral absorption enhancers for hydrophilic macromolecules by electrostatic or covalent conjugation on in conjunction with nanotechnology. Endogenous cellular uptake mechanisms present in the intestine can be exploited by engineering peptide conjugates that transcytose; entering cells by endocytosis and leaving by exocytosis...
February 2018: Peptides
Ryo Masuda, Risa Hayashi, Hiroshi Nose, Akihiro Taguchi, Yoshio Hayashi, Hiroyuki Yasui, Takaki Koide
AIM: The development of a platinum anticancer agent that has improved efficacy by efficient delivery to a tumor and that suppresses side effects has been investigated. Arginine-rich triple-helical peptides are promising drug carriers because of their stability in body fluids and cell-penetrating activity. RESULTS: We synthesized a carboplatin derivative conjugated with an arginine-rich triple-helical peptide. This derivative released platinum under acidic conditions or in the presence Cl- ions...
February 7, 2018: Future Medicinal Chemistry
Weijing Yang, Liang Yang, Yifeng Xia, Liang Cheng, Jian Zhang, Fenghua Meng, Jiandong Yuan, Zhiyuan Zhong
Lung cancer is one of the worldwide leading and fast-growing malignancies. Pemetrexed disodium (PEM, Alimta®), a small hydrophilic drug, is currently used for treating lung cancer patients. However, PEM suffers from issues like fast elimination, low bioavailability, poor tumor cell selectivity and penetration. Here, we report on lung cancer specific CSNIDARAC (CC9) peptide-functionalized reduction-responsive chimaeric polymersomes (CC9-RCPs) for efficient encapsulation and targeted delivery of PEM to H460 human lung cancer cells in vitro and in vivo...
February 2, 2018: Acta Biomaterialia
Takuya Ishikawa, Kana Somiya, Reina Munechika, Hideyoshi Harashima, Yuma Yamada
To achieve mitochondrial gene therapy, developing a mitochondrial transgene expression system that produces therapeutic proteins in mitochondria of disease cells is essential. We previously reported on the design of pCMV-mtLuc (CGG) containing a CMV promotor and a NanoLuc (Nluc) luciferase gene that records adjustments to the mitochondrial codon system, and showed that the mitochondrial transfection of pCMV-mtLuc (CGG) resulted in the efficient production of the Nluc luciferase protein in human HeLa cells. This mitochondrial transfection was achieved using a MITO-Porter, a liposome-based carrier for delivering a cargo to mitochondria via membrane fusion...
February 3, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Steven Droho, Mitchell E Keener, Niklaus H Mueller
No abstract text is available yet for this article.
January 31, 2018: Biochimica et Biophysica Acta
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