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cellular uptake

Qing Hu, Qing Chen, Xiuyun Yan, Bomei Ding, Dawei Chen, Lifang Cheng
AIM: To develop a nanocarrier for targeted delivery of agents to the cartilage. MATERIALS & METHODS: Chondrocyte affinity peptide modified PEGylated polyamidoamine conjugates (CAP-PEG-PAMAM) were prepared and rhodamine B isothiocyanate (RB) fluorophore was linked on them for comparative biological tracing and profiling. RESULTS: CAP4-PP-RB exhibited much more efficient cellular uptake in vitro than that of PEG-PAMAM-RB. Both the conjugates were likely internalized by chondrocytes via clathrin and caveolin co-mediated endocytosis, and delivered to lysosomes...
March 12, 2018: Nanomedicine
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
Della S Shin, Emi Y Tokuda, Jennifer L Leight, Connor E Miksch, Tobin E Brown, Kristi S Anseth
Proteases are involved in almost every important cellular activity, from embryonic morphogenesis to apoptosis. To study protease activity in situ , hydrogels provide a synthetic mimic of the extracellular matrix (ECM) and have utility as a platform to study activity, such as those related to cell migration, in three-dimensions. While 3-dimensional visualization of protease activity could prove quite useful to elucidate the proteolytic interaction at the interface between cells and their surrounding environment, there has been no versatile tool to visualize local proteolytic activity in real time...
2018: ACS Biomaterials Science & Engineering
Vladimir Kepe, Claudio Scafoglio, Jie Liu, William H Yong, Marvin Bergsneider, Sung-Cheng Huang, Jorge R Barrio, Ernest M Wright
A novel glucose transporter, the sodium glucose cotransporter 2 (SGLT2), has been demonstrated to contribute to the demand for glucose by pancreatic and prostate tumors, and its functional activity has been imaged using a SGLT specific PET imaging probe, α-methyl-4-[F-18]fluoro-4-deoxy-D-glucopyaranoside (Me-4FDG). In this study, Me-4FDG PET was extended to evaluate patients with high-grade astrocytic tumors. Me-4FDG PET scans were performed in four patients diagnosed with WHO Grade III or IV astrocytomas and control subjects, and compared with 2-deoxy-2-[F-18]fluoro-D-glucose (2-FDG) PET and magnetic resonance imaging (MRI) of the same subjects...
March 10, 2018: Journal of Neuro-oncology
Hao Shi, Alexander Munk, Thomas S Nielsen, Morgan R Daughtry, Louise Larsson, Shize Li, Kasper F Høyer, Hannah W Geisler, Karolina Sulek, Rasmus Kjøbsted, Taylor Fisher, Marianne M Andersen, Zhengxing Shen, Ulrik K Hansen, Eric M England, Zhiyong Cheng, Kurt Højlund, Jørgen F P Wojtaszewski, Xiaoyong Yang, Matthew W Hulver, Richard F Helm, Jonas T Treebak, David E Gerrard
OBJECTIVE: Given that cellular O-GlcNAcylation levels are thought to be real-time measures of cellular nutrient status and dysregulated O-GlcNAc signaling is associated with insulin resistance, we evaluated the role of O-GlcNAc transferase (OGT), the enzyme that mediates O-GlcNAcylation, in skeletal muscle. METHODS: We assessed O-GlcNAcylation levels in skeletal muscle from obese, type 2 diabetic people, and we characterized muscle-specific OGT knockout (mKO) mice in metabolic cages and measured energy expenditure and substrate utilization pattern using indirect calorimetry...
February 24, 2018: Molecular Metabolism
Lauren E Jamieson, Jennifer Greaves, Jayde A McLellan, Kevin R Munro, Nicholas C O Tomkinson, Luke H Chamberlain, Karen Faulds, Duncan Graham
Intracellular uptake, distribution and metabolism of lipids are tightly regulated characteristics in healthy cells. An analytical technique capable of understanding these characteristics with a high level of species specificity in a minimally invasive manner is highly desirable in order to understand better how these become disrupted during disease. In this study, the uptake and distribution of three different alkyne tagged fatty acids in single cells were monitored and compared, highlighting the ability of Raman spectroscopy combined with alkyne tags for better understanding of the fine details with regard to uptake, distribution and metabolism of very chemically specific lipid species...
March 7, 2018: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
Yanxue Liu, Kefeng Liu, Xiaomin Li, Shangzhen Xiao, Dan Zheng, Pengbo Zhu, Chunxiao Li, Jing Liu, Jing He, Jiandu Lei, Luying Wang
The application of non-toxic carriers to increase drug loading, multi-drug delivery, and extremely small size of nano-drugs to construct a tremendous transmission system is the goal for all researchers to be pursued. The proposal of natural pectin nano-platform for delivery of multiple drugs is critical for biomedical research, especially a particle size of below 100nm with high yield. Here we design a new core-shell structure pectin-eight-arm polyethylene glycol-ursolic acid/hydrooxycampothecin nanoparticle (Pec-8PUH NPs) through a special self-assembly method for stabilizing and dispersing particles, improving water-solubility, and achieving drug controlled release...
May 1, 2018: Materials Science & Engineering. C, Materials for Biological Applications
Hironori Nagasaka, Ken-Ichi Hirano, Tohru Yorifuji, Haruki Komatsu, Tomonozumi Takatani, Ichiro Morioka, Satoshi Hirayama, Takashi Miida
OBJECTIVE: CD36 deficiency is characterized by limited cellular long chain fatty acid uptake in the skeletal and cardiac muscles and often causes energy crisis in these muscles. However, suitable treatment for CD36 deficiency remains to be established. The aim of this study was to evaluate the clinical and metabolic effects of medium chain triacylglycerols (MCTs) in two CD36-deficient preschool children who often developed fasting hypoglycemia and exercise-induced myalgia. METHODS: Fasting blood glucose, total ketone bodies, and free fatty acids were examined and compared for usual supper diets and for diets with replacement of one component with 2 g/kg of 9% MCT-containing milk (MCT milk)...
November 29, 2017: Nutrition
Mickaël F El Hachmane, Charlotta S Olofsson
Ca2+ impacts a large array of cellular processes in every known cell type. In the white adipocyte, Ca2+ is involved in regulation of metabolic processes such as lipolysis, glucose uptake and hormone secretion. Although the importance of Ca2+ in control of white adipocyte function is clear, knowledge is still lacking regarding the control of dynamic Ca2+ alterations within adipocytes and mechanisms inducing intracellular Ca2+ changes remain elusive. Own work has recently demonstrated the existence of store-operated Ca2+ entry (SOCE) in lipid filled adipocytes...
March 7, 2018: Biochemical and Biophysical Research Communications
Jingjie Tan, Chan Li, Qian Wang, Shuyi Li, Shizhu Chen, Jinchao Zhang, Paul C Wang, Lei Ren, Xing-Jie Liang
Flurbiprofen, a hydrophobic COX inhibitor, was coordinated axially with oxoplatin to form a new conjugate cis, cis, trans-[Pt(IV)(NH3)2Cl2(flurbiprofen)2]. The successful synthsis of this new conjugate was confirmed by 1H, 13C and 195Pt NMR. The potential of this conjugate being reduced to cisplatin and subsequently exerting its DNA cross-linking ability was verified using cyclic voltammetry (CV), HPLC and mass spectrum (MS). This conjugate showed markedly higher cytotoxicity on many cancer cell lines than cisplatin, flurbiprofen and physical mixture (mol ratio, cisplatin: flurbiprofen=1:2) of them...
March 9, 2018: Molecular Pharmaceutics
Seyed Jalal Hosseinimehr, Sajjad Ahmadpour, Zohraeh Noaparast, Seyed Mohamamd Abedi
BACKGROUND: Breast cancer is malignant disease with high mortality rate among women in the world. It is necessary to diagnose breast cancer at the early stage before it metastasizes in patients. OBJECTIVE: The aim of this is the evaluation of 99mTc-(tricine)-HYNIC-Lys-FROP for breast tumor imaging. METHOD: Lys-FROP peptide was labeled with 99mTc using HYNIC as chelator and tricine as co-ligand. Specific binging of this radiolabeled peptide on breast cancerous cell was assessed in different cell lines as well as in tumor bearing mice...
March 7, 2018: Anti-cancer Agents in Medicinal Chemistry
Rei Nagahara, Nobuhiko Onda, Susumu Yamashita, Miho Kojima, Mari Inohana, Ayumi Eguchi, Misato Nakamura, Shinya Matsumoto, Toshinori Yoshida, Makoto Shibutani
Fluorescence tumor imaging using exogenous fluorescent tumor-targeting agents has potential to improve early tumor detection. The fluorescent contrast agent indocyanine green (ICG) is used in medical diagnostics. The aim of the present study is to investigate the tumor imaging capability and the imaging mechanism of i.v. administered ICG in a mouse model of colitis-associated colon cancer. To do this, an azoxymethane/dextran sodium sulfate-induced colon cancer mouse model was used. Ex vivo imaging experiments were performed 1 hour after i...
March 9, 2018: Cancer Science
Junaid Afzal, Angel Chan, Mehmet Fatih Karakas, Kirubel Woldemichael, Styliani Vakrou, Yufan Guan, Jeffrey Rathmell, Richard Wahl, Martin Pomper, D Brian Foster, Miguel A Aon, Benjamin Tsui, Brian O'Rourke, M Roselle Abraham
Adult stem cells demonstrate metabolic flexibility that is regulated by cell adhesion status. The authors demonstrate that adherent cells primarily utilize glycolysis, whereas suspended cells rely on oxidative phosphorylation for their ATP needs. Akt phosphorylation transduces adhesion-mediated regulation of energy metabolism, by regulating translocation of glucose transporters (GLUT1) to the cell membrane and thus, cellular glucose uptake and glycolysis. Cell dissociation, a pre-requisite for cell transplantation, leads to energetic stress, which is mediated by Akt dephosphorylation, downregulation of glucose uptake, and glycolysis...
October 2017: JACC. Basic to Translational Science
Changqie Pan, Yuqing Liu, Minyu Zhou, Wensheng Wang, Min Shi, Malcolm Xing, Wangjun Liao
A multifunctional theranostic nanoplatform integrated with environmental responses has been developed rapidly over the past few years as a novel treatment strategy for several solid tumors. We synthesized pH-sensitive poly(β-thiopropionate) nanoparticles with a supermagnetic core and folic acid (FA) conjugation (FA-doxorubicin-iron oxide nanoparticles [FA-DOX@ IONPs]) to deliver an antineoplastic drug, DOX, for the treatment of folate receptor (FR)-overexpressed breast cancer. In addition to an imaging function, the nanoparticles can release their payloads in response to an environment of pH 5, such as the acidic environment found in tumors...
2018: International Journal of Nanomedicine
M Leontien van der Bent, Omar Paulino da Silva Filho, Judith van Luijk, Roland Brock, Derick G Wansink
Antisense oligonucleotide (AON)-based therapies hold promise for a range of neurodegenerative and neuromuscular diseases and have shown benefit in animal models and patients. Success in the clinic is nevertheless still limited, due to unfavourable biodistribution and poor cellular uptake of AONs. Extensive research is currently being conducted into the formulation of AONs to improve delivery, but thus far there is no consensus on which of those strategies will be the most effective. This systematic review was designed to answer in an unbiased manner which delivery strategies most strongly enhance the efficacy of AONs in animal models of heritable neurodegenerative and neuromuscular diseases...
March 8, 2018: Scientific Reports
Peiqi Zhao, Lanfang Li, Shiyong Zhou, Lihua Qiu, Zhengzi Qian, Xianming Liu, Xuchen Cao, Huilai Zhang
Multidrug resistance (MDR) has become a very serious problem in cancer therapy. To effectively reverse MDR in tumor treatments, a new pH-sensitive nano drug delivery system (NDDS) composed of mesoporous silica nanoparticles (MSNs) and d-a-tocopheryl poly-ethylene glycol 1000 succinate (TPGS) copolymers was synthesized to deliver doxorubicin (DOX) into drug-resistant breast cancer cell line (MCF-7/ADR). DOX@MSNs-TPGS were characterized to have a single peak size distribution, high DOX loading efficiency and a pH-dependent drug release profile...
March 1, 2018: Materials Science & Engineering. C, Materials for Biological Applications
Rui-Jun Ju, Li-Min Mu, Xue-Tao Li, Cui-Qing Li, Zhan-Jie Cheng, Wan-Liang Lu
The efficacy of anticancer drugs is rather limited in the treatment of brain glioma due to the hindrance of the blood-brain barrier (BBB). Herein, we reported an easy formulation of functional docetaxel nanomicelles for the treatment of brain glioma using a graft copolymer soluplus as basic material through dual-modifications with a glucose-lipid derivative and a dequalinium-lipid derivative. The studies were performed on brain glioma U87MG cells, in vitro BBB models and brain glioma-bearing nude mice. The functional docetaxel nanomicelles were approximately 100 nm...
March 8, 2018: Artificial Cells, Nanomedicine, and Biotechnology
Mona Alibolandi, Khalil Abnous, Sajjad Anvari, Marzieh Mohammadi, Mohammad Ramezani, Seyed Mohammad Taghdisi
Poor aqueous solubility of chemotherapeutics such as SN38 (7-ethyl-10-hydroxycamptothecin) and the associated systemic adverse effects are serious limitations of their clinical use. To improve the drug delivery efficiency of such compounds, they were covalently conjugated to hydrophilic macromolecular carriers that specifically deliver the drug moiety to the tumour cells. In the current study, we developed a PEGylated acetylated carboxymethylcellulose conjugate of SN38 which was covalently attached to an aptamer against a cancer stem cell marker, CD133...
March 8, 2018: Artificial Cells, Nanomedicine, and Biotechnology
Maia Kavanagh Williamson, Naomi Coombes, Florian Juszczak, Marios Athanasopoulos, Mariam B Khan, Thomas R Eykyn, Ushani Srenathan, Leonie S Taams, Julianna Dias Zeidler, Andrea T Da Poian, Hendrik Huthoff
Infection of primary CD4+ T cells with HIV-1 coincides with an increase in glycolysis. We investigated the expression of glucose transporters (GLUT) and glycolytic enzymes in human CD4+ T cells in response to infection with HIV-1. We demonstrate the co-expression of GLUT1, GLUT3, GLUT4, and GLUT6 in human CD4+ T cells after activation, and their concerted overexpression in HIV-1 infected cells. The investigation of glycolytic enzymes demonstrated activation-dependent expression of hexokinases HK1 and HK2 in human CD4+ T cells, and a highly significant increase in cellular hexokinase enzyme activity in response to infection with HIV-1...
March 7, 2018: Viruses
Angela D'Ascola, Giuseppe Bruschetta, Gabriella Zanghì, Salvatore Campo, Pietro Medica, Stefania Campana, Guido Ferlazzo, Bernhard F Gibbs, Alida Maria Ferlazzo
Serotonin (5-HT) is a neurohormone transported from plasma into platelets and leukocytes by a specific transporter (SERT). While it is known that the brain 5-HT system is modulated by physical exercise, the peripheral serotoninergic response to exercise is not yet fully elucidated. In particular, this study aimed to evaluate changes in plasma 5-HT levels and equine leukocyte SERT expression in response to treadmill exercise in untrained horses. Analyses were carried out pre- and post-treadmill exercise. 5-HT plasma levels were analysed by HPLC...
February 27, 2018: Research in Veterinary Science
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