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https://www.readbyqxmd.com/read/28821028/targeted-gene-delivery-of-polyethyleneimine-grafted-chitosan-with-rgd-dendrimer-peptide-in-%C3%AE-v%C3%AE-3-integrin-overexpressing-tumor-cells
#1
Young-Min Kim, Seong-Cheol Park, Mi-Kyeong Jang
The safe and effective delivery of genetic material into cells is a necessary factor for gene therapy. Although a wide range of materials, methods, and combinations have been reported, successful gene therapy has been limited. In the present study, a targeted gene carrier for αvβ3 integrin-overexpressing tumor cells was designed using widely applied materials containing water soluble chitosan (WSC), RGD peptide, and polyethyleneimine (PEI). The physiological characteristics, in vitro targeted gene transfection, cytotoxicity, blood-compatibility, and cellular distributions were investigated...
October 15, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28817973/the-agma1-polyamidoamine-mediates-the-efficient-delivery-of-sirna
#2
Roberta Cavalli, Luca Primo, Roberto Sessa, Giulia Chiaverina, Laura di Blasio, Jenny Alongi, Amedea Manfredi, Elisabetta Ranucci, Paolo Ferruti
AGMA1, a prevailingly cationic, guanidine-bearing, linear, amphoteric polyamidoamine is an effective siRNA condensing agent. Here two AGMA1 samples of different molecular weight, i.e. AGMA1-5 and AGMA1-10 were evaluated as siRNA condensing agents and transfection promoters. AGMA1-10 formed stable polyplexes with a size lower than 50 nm and positive zeta potential. AGMA1-5 polyplexes were larger, about 100 nm in size. AGMA1-10 polyplexes, but not AGMA1-5 proved to be an effective intracellular siRNA carrier, able to trigger gene silencing in Hela and PC3 cell lines without eliciting cytotoxic effects...
August 18, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28811617/cell-surface-binding-uptaking-and-anticancer-activity-of-l-k6-a-lysine-leucine-rich-peptide-on-human-breast-cancer-mcf-7-cells
#3
Che Wang, Shaodan Dong, Lin Zhang, Ying Zhao, Lili Huang, Xiange Gong, He Wang, Dejing Shang
Cell surface binding and internalization are critical for the specific targeting and biofunctions of some cationic antimicrobial peptides (CAPs) with anticancer activities. However, the detailed cellular process for CAPs interacting with cancer cells and the exact molecular basis for their anticancer effects are still far from being fully understood. In the present study, we examined the cell surface binding, uptaking and anti-cancer activity of L-K6, a lysine/leucine-rich CAP, in human MCF-7 breast cancer cells...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28799243/escherichia-coli-k1-utilises-host-macropinocytic-pathways-for-invasion-of-brain-microvascular-endothelial-cells
#4
Lip Nam Loh, Elizabeth M C McCarthy, Priyanka Narang, Naveed A Khan, Theresa H Ward
Eukaryotic cells utilise multiple endocytic pathways for specific uptake of ligands or molecules, and these pathways are commonly hijacked by pathogens to enable host cell invasion. Escherichia coli K1, a pathogenic bacterium that causes neonatal meningitis, invades the endothelium of the blood-brain barrier, but the entry route remains unclear. Here we demonstrate that the bacteria trigger an actin-mediated uptake route, stimulating fluid phase uptake, membrane ruffling and macropinocytosis. The route of uptake requires intact lipid rafts as shown by cholesterol depletion...
August 11, 2017: Traffic
https://www.readbyqxmd.com/read/28757359/identification-of-cyclic-peptides-for-facilitation-of-transcellular-transport-of-phages-across-intestinal-epithelium-in-vitro-and-in-vivo
#5
Shunsuke Yamaguchi, Shingo Ito, Mio Kurogi-Hirayama, Sumio Ohtsuki
Methodology to enhance intestinal absorption of macromolecular drugs is an important challenge for developing next-generation biomedicines. So far, various cationic cell-penetrating peptides have been reported to facilitate uptake of certain bioactive proteins. However, cyclic peptides might be better candidates, as they are more metabolically stable than linear peptides. Accordingly, we hypothesized that suitable cyclic peptides would promote the absorption of macromolecules across intestinal epithelium. To test this idea, we adopted Caco-2 cell permeability assay as an in vitro human intestinal absorption model, and M13 phage as a model of macromolecules...
July 27, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28754944/cytosolic-antibody-delivery-by-lipid-sensitive-endosomolytic-peptide
#6
Misao Akishiba, Toshihide Takeuchi, Yoshimasa Kawaguchi, Kentarou Sakamoto, Hao-Hsin Yu, Ikuhiko Nakase, Tomoka Takatani-Nakase, Fatemeh Madani, Astrid Gräslund, Shiroh Futaki
One of the major obstacles in intracellular targeting using antibodies is their limited release from endosomes into the cytosol. Here we report an approach to deliver proteins, which include antibodies, into cells by using endosomolytic peptides derived from the cationic and membrane-lytic spider venom peptide M-lycotoxin. The delivery peptides were developed by introducing one or two glutamic acid residues into the hydrophobic face. One peptide with the substitution of leucine by glutamic acid (L17E) was shown to enable a marked cytosolic liberation of antibodies (immunoglobulins G (IgGs)) from endosomes...
August 2017: Nature Chemistry
https://www.readbyqxmd.com/read/28724764/rab5-and-rab11-are-required-for-clathrin-dependent-endocytosis-of-japanese-encephalitis-virus-in-bhk-21-cells
#7
Chun-Chun Liu, Yun-Na Zhang, Zhao-Yao Li, Jin-Xiu Hou, Jing Zhou, Lin Kan, Bin Zhou, Pu-Yan Chen
During infection Japanese Encephalitis Virus generally enters host cells via receptor-mediated clathrin dependent endocytosis. The trafficking of JEV within endosomes is controlled by Rab GTPases, but which Rab proteins are involved in JEV entry into BHK-21 cells is unknown. In this study, entry and post-internalization of JEV were analyzed using biochemical inhibitors, RNA interference and dominant negative mutants. Our data demonstrate that JEV entry into BHK-21 cells depends on clathrin, dynamin, and cholesterol, but not caveolae or macropinocytosis...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28717157/cellular-uptake-pathways-of-sepiolite-nanofibers-and-dna-transfection-improvement
#8
Fidel Antonio Castro-Smirnov, Jeanne Ayache, Jean-Rémi Bertrand, Elodie Dardillac, Eric Le Cam, Olivier Piétrement, Pilar Aranda, Eduardo Ruiz-Hitzky, Bernard S Lopez
Sepiolite is a nanofibrous natural silicate that can be used as a nanocarrier because it can be naturally internalized into mammalian cells, due to its nano-size dimension. Therefore, deciphering the mechanisms of sepiolite cell internalization constitutes a question interesting biotechnology, for the use of sepiolite as nanocarrier, as well as environmental and public health concerns. Though it is low, the perfectly stable and natural intrinsic fluorescence of sepiolite nanofibers allows to follow their fate into cells by specifically sensitive technics...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28713017/intracellular-co-delivery-of-sr-ion-and-phenamil-drug-through-mesoporous-bioglass-nanocarriers-synergizes-bmp-signaling-and-tissue-mineralization
#9
Jung-Hwan Lee, Nandin Mandakhbayar, Ahmed El-Fiqi, Haw-Won Kim
Inducing differentiation and maturation of resident multipotent stem cells (MSCs) is an important strategy to regenerate hard tissues in mal-calcification conditions. Here we explore a co-delivery approach of therapeutic molecules comprised of ion and drug through a mesoporous bioglass nanoparticle (MBN) for this purpose. Recently, MBN has offered unique potential as a nanocarrier for hard tissues, in terms of high mesoporosity, bone bioactivity (and possibly degradability), tunable delivery of biomolecules, and ionic modification...
July 13, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28694083/impact-of-surface-functionalization-on-the-uptake-mechanism-and-toxicity-effects-of-silver-nanoparticles-in-hepg2-cells
#10
Lada Brkić Ahmed, Mirta Milić, Igor M Pongrac, Ana Marija Marjanović, Hrvoje Mlinarić, Ivan Pavičić, Srećko Gajović, Ivana Vinković Vrček
Safe and successful bioapplications of metallic nanoparticles depend on their physicochemical characteristics, in particular their surface properties. This study aimed to investigate how different surface functionalization of silver nanoparticles (AgNP) affect their interaction with mammalian liver cells with regard to cytotoxicity, genotoxicity and mechanism of cellular uptake. Differentially coated AgNP were prepared by surface functionalization using sodium bis(2-ethylhexyl)-sulfosuccinate (AOTAgNP), cetyltrimethylammonium bromide (CTABAgNP), poly(vinylpyrrolidone) (PVPAgNP), poly-l-lysine (PLLAgNP), and bovine serum albumin (BSAAgNP)...
September 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28686970/endocytic-pathways-of-optimized-resveratrol-cubosomes-capturing-into-human-hepatoma-cells
#11
Hend Mohamed Abdel-Bar, Rania Abd El Basset Sanad
Resveratrol (RSV) is a natural polyphenolic compound with high affinity to hepatocytes. It has numerous benefits as anticancer, antioxidant, immunomodulatory and cardioprotective actions. Nevertheless, RSV therapeutic applications are hindered by its low solubility, light sensitivity and extensive first-pass metabolism. Cubosomes are colloidally stable dispersed liquid crystalline nanoparticles. The incorporation of RSV into cubosomes could overcome some of its physicochemical limitations. A Design-Expert(®) software was applied to optimize cubosomes in terms of particle size and encapsulation efficiency (EE%)...
September 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28678485/an-ursolic-acid-derived-small-molecule-triggers-cancer-cell-death-through-hyperstimulation-of-macropinocytosis
#12
Lin Sun, Bin Li, Xiaohui Su, Ge Chen, Yaqin Li, Linqian Yu, Li Li, Wanguo Wei
Macropinocytosis is a transient endocytosis that internalizes extracellular fluid and particles into vacuoles. Recent studies suggest that hyperstimulation of macropinocytosis can induce a novel nonapoptotic cell death, methuosis. In this report, we describe the identification of an ursolic acid derived small molecule (compound 17), which induces cancer cell death through hyperstimulation of macropinocytosis. 17 causes the accumulation of vacuoles derived from macropinosomes based on transmission electron microscopy, time-lapse microscopy, and labeling with extracellular fluid phase tracers...
July 19, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28664153/sopb-mediated-recruitment-of-snx18-facilitates-salmonella-typhimurium-internalization-by-the-host-cell
#13
David Liebl, Xiaying Qi, Yang Zhe, Timothy C Barnett, Rohan D Teasdale
To invade epithelial cells, Salmonella enterica serovar Typhimurium (S. Typhimurium) induces macropinocytosis through the action of virulence proteins delivered across the host cell membrane via a type III secretion system. We show that after docking at the plasma membrane S. Typhimurium triggers rapid recruitment of cytosolic SNX18, a SH3-PX-BAR domain sorting nexin protein, to the bacteria-induced membrane ruffles and to the nascent Salmonella-containing vacuole. SNX18 recruitment required the inositol-phosphatase activity of the Salmonella effector SopB and an intact phosphoinositide-binding site within the PX domain of SNX18, but occurred independently of Rho-GTPases Rac1 and Cdc42 activation...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28663722/bacoside-a-induces-tumor-cell-death-in-human-glioblastoma-cell-lines-through-catastrophic-macropinocytosis
#14
Sebastian John, K C Sivakumar, Rashmi Mishra
Glioblastoma multiforme (GBM) is a highly aggressive type of brain tumor with an extremely poor prognosis. Recent evidences have shown that the "biomechanical imbalances" induced in GBM patient-derived glioblastoma cells (GC) and in vivo via the administration of synthetic small molecules, may effectively inhibit disease progression and prolong survival of GBM animal models. This novel concept associated with de novo anti-GBM drug development has however suffered obstacles in adequate clinical utility due to the appearance of unrelated toxicity in the prolonged therapeutic windows...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28659379/glutamine-fuels-proliferation-but-not-migration-of-endothelial-cells
#15
Boa Kim, Jia Li, Cholsoon Jang, Zoltan Arany
Endothelial metabolism is a key regulator of angiogenesis. Glutamine metabolism in endothelial cells (ECs) has been poorly studied. We used genetic modifications and (13)C tracing approaches to define glutamine metabolism in these cells. Glutamine supplies the majority of carbons in the tricyclic acid (TCA) cycle of ECs and contributes to lipid biosynthesis via reductive carboxylation. EC-specific deletion in mice of glutaminase, the initial enzyme in glutamine catabolism, markedly blunts angiogenesis. In cell culture, glutamine deprivation or inhibition of glutaminase prevents EC proliferation, but does not prevent cell migration, which relies instead on aerobic glycolysis...
August 15, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28655784/inhibition-of-megakaryocyte-differentiation-by-antibody-drug-conjugates-adcs-is-mediated-by-macropinocytosis-implications-for-adc-induced-thrombocytopenia
#16
Hui Zhao, Sara Gulesserian, Sathish Kumar Ganesan, Jimmy Ou, Karen Morrison, Zhilan Zeng, Veronica Robles, Josh Snyder, Lisa Do, Hector Aviña, Sher Karki, David R Stover, Fernando Doñate
Thrombocytopenia is a common adverse event in cancer patients treated with antibody-drug conjugates (ADCs), including AGS-16C3F, an ADC targeting ENPP3 (ectonucleotide pyrophosphatase/phosphodiesterase-3) and Trastuzumab emtansine (T-DM1). This study aims to elucidate the mechanism of action of ADC-induced thrombocytopenia. ENPP3 expression in platelets and megakaryocytes (MKs) was investigated and shown to be negative. The direct effect of AGS-16C3F on platelets was evaluated using platelet rich plasma following the expression of platelet activation markers...
June 27, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28655275/nontransformed-and-cancer-cells-can-utilize-different-endocytic-pathways-to-internalize-dendritic-nanoparticle-variants-implications-on-nanocarrier-design
#17
Nelson K Y Wong, Rajesh A Shenoi, Srinivas Abbina, Irina Chafeeva, Jayachandran N Kizhakkedathu, Mohamed K Khan
Three hyperbranched polyglycerol nanoparticle (HPG NP) variants were synthesized and fluorescently labeled for the study of their cellular interactions. The polymeric nanoparticle that contains a hydrophobic core and a hydrophilic HPG shell, HPG-C10-HPG, is taken up faster by HT-29 cancer cells than nontransformed cells, while similar uptake rates are observed with both cell types for the nanoparticle HPG-C10-PEG that contains a hydrophobic core and a polyethylene glycol shell. The nanoparticle HPG-104, containing neither the hydrophobic core nor the polyethylene glycol shell, is taken up faster by nontransformed cells than HT-29 cells...
July 17, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28651541/the-agglomeration-state-of-nanoparticles-can-influence-the-mechanism-of-their-cellular-internalisation
#18
Blanka Halamoda-Kenzaoui, Mara Ceridono, Patricia Urbán, Alessia Bogni, Jessica Ponti, Sabrina Gioria, Agnieszka Kinsner-Ovaskainen
BACKGROUND: Significant progress of nanotechnology, including in particular biomedical and pharmaceutical applications, has resulted in a high number of studies describing the biological effects of nanomaterials. Moreover, a determination of so-called "critical quality attributes", that is specific physicochemical properties of nanomaterials triggering the observed biological response, has been recognised as crucial for the evaluation and design of novel safe and efficacious therapeutics...
June 26, 2017: Journal of Nanobiotechnology
https://www.readbyqxmd.com/read/28637475/uptake-of-label-free-graphene-oxide-by-caco-2-cells-is-dependent-on-the-cell-differentiation-status
#19
Melanie Kucki, Liliane Diener, Nils Bohmer, Cordula Hirsch, Harald F Krug, Vincenzo Palermo, Peter Wick
BACKGROUND: Understanding the interaction of graphene-related materials (GRM) with human cells is a key to the assessment of their potential risks for human health. There is a knowledge gap regarding the potential uptake of GRM by human intestinal cells after unintended ingestion. Therefore the aim of our study was to investigate the interaction of label-free graphene oxide (GO) with the intestinal cell line Caco-2 in vitro and to shed light on the influence of the cell phenotype given by the differentiation status on cellular uptake behaviour...
June 21, 2017: Journal of Nanobiotechnology
https://www.readbyqxmd.com/read/28634138/intracellular-and-transdermal-protein-delivery-mediated-by-non-covalent-interactions-with-a-synthetic-guanidine-rich-molecular-carrier
#20
Jungkyun Im, Sanket Das, Dongjun Jeong, Chang-Jin Kim, Hyun-Suk Lim, Ki Hean Kim, Sung-Kee Chung
The impermeability of the cell plasma membrane is one of the major barriers for protein transduction into mammalian cells, and it also limits the use of proteins as therapeutic agents. Protein transduction has usually been achieved based on certain invasive processes or cell penetrating peptides (CPP). Herein we report our study in which a synthetic guanidine-rich molecular carrier is used as a delivery vector for intracellular and transdermal delivery of proteins. First a sorbitol-based molecular carrier having 8 guanidine units (Sor-G8) was synthesized, and then was simply mixed with a cargo protein of varying sizes to form the non-covalent complex of carrier-cargo proteins...
August 7, 2017: International Journal of Pharmaceutics
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