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Endosomes Cancer

Kevin Ho, Cristobal Morfin, Katarzyna Slowinska
The in vitro efficacy of cancer prodrugs varies significantly between malignant cell lines. The most commonly identified problems relate to delivery: uptake mechanism, endosomal entrapment, and drug release. Here we present the study of collagen/cell penetrating hybrid (COL/CPP) peptide carriers intended to deliver paclitaxel to the hypopharyngeal carcinoma (FaDu) cells. Confocal microscopy imaging revealed the surprising response of FaDu cell to COL/CPP in comparison to previously studied cancer cell lines: hybrid peptides that carry both COL and CPP domain adsorb on the FaDu cell surface...
February 14, 2019: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Kyung Hwa Cho, Hoi Young Lee
Cancer invasion and metastasis is the crucial cause of death for most cancer patients. Endosome recycling of receptors for growth factors and adhesion molecules to the plasma membrane prevents them from degradation at the inside of the lysosome and recapitulates their functions, leading to major causativeness of cancer progression. Rab25 belongs to Rab-GTPase family and implicated in cancer progression in a context-dependent manner. Identified as a binding partner of Rab25, Rab coupling protein (RCP) augments cancer invasion and metastasis...
February 14, 2019: Archives of Pharmacal Research
Pei Liu, Jinghua Ren, Yuxuan Xiong, Zhe Yang, Wei Zhu, Qianyuan He, Zushun Xu, Wenshan He, Jing Wang
Mitochondria, which are a major source of adenosine triphosphate (ATP) and apoptosis regulators, are the key organelles that promote tumor cell proliferation, and their dysfunction affects tumor cell behavior. Additionally, mitochondria have been shown to play a central role in the biosynthesis of protoporphyrin IX (PpIX), which is a widely used photosensitizer that has been used for tumor detection, monitoring and photodynamic therapy. Nevertheless, photosensitizers administrated exogenously are often restricted by limited bioavailability...
February 2, 2019: Biomaterials
Wei Li, Liyuan Zhang, Binbin Guo, Jieqiong Deng, Siqi Wu, Fang Li, Yirong Wang, Jiachun Lu, Yifeng Zhou
BACKGROUND: Though esophageal cancer is three to four times more common among males than females worldwide, this type of cancer still ranks in the top incidence among women, even more than the female specific cancer types. The occurrence is currently attributed to extrinsic factors, including tobacco use and alcohol consumption. However, limited attention has been given to gender-specific intrinsic genetic factors, especially in female. METHODS: We re-annotated a large cohort of microarrays on 179 ESCC patients and identified female-specific differently expressed lncRNAs...
February 8, 2019: Molecular Cancer
Ajmeeta Sangtani, Eleonora Petryayeva, Kimihiro Susumu, Eunkeu Oh, Alan L Huston, Guillermo Lasarte-Aragones, Igor L Medintz, W Russ Algar, James B Delehanty
Multidrug resistance (MDR) is a significant challenge in the treatment of many types of cancers as membrane-associated transporters actively pump drugs out of the cell, limiting therapeutic efficacy. While nanoparticle (NP)-based therapeutics have emerged as a mechanism for overcoming MDR, they often rely on the delivery of multiple anticancer drugs, nucleic acid hybrids, or MDR pump inhibitors. The effectiveness of these strategies, however, can be limited by their off-target toxicity or the need for genetic transfection...
February 8, 2019: Bioconjugate Chemistry
Yihua Yang, Zhe Wang, Ying Peng, Jinsong Ding, Wenhu Zhou
Micelles are highly attractive nano-drug delivery systems for targeted cancer therapy. While they have been demonstrated to significantly alleviate the side-effects of their cargo drugs, the therapy outcomes are usually suboptimal partially due to ineffective drug release and endosome entrapment. Stimulus-responsive nanoparticles have allowed controlled drug release in a smart fashion, and we want to use this concept to design novel micelles. Herein, we reported pH-sensitive paclitaxel (PTX)-loaded poly (ethylene glycol)-phenylhydrazone-dilaurate (PEG-BHyd-dC12 ) micelles (PEG-BHyd-dC12 /PTX)...
2019: Frontiers in Pharmacology
Zheyu Song, Xiao Liang, Yudi Wang, Haobo Han, Jiebing Yang, Xuedong Fang, Quanshun Li
In the present research, a tumor-targeted gene carrier, PPP, was constructed through the modification of phenylboronic acid onto the surface of a polyamidoamine dendrimer, and then miR-34a delivery was employed as a model to evaluate its anti-tumor efficacy. The carrier PPP was identified to possess favorable miR-34a binding and condensation ability and meanwhile protect miR-34a against nuclease degradation. Through confocal laser scanning microscopy and flow cytometry analysis, PPP-mediated cellular uptake of miR-34a was found to proceed through a sialic acid-dependent endocytosis pathway and the nanoparticles could achieve endosome/lysosome escape within 6 h...
February 5, 2019: Biomaterials Science
Asma'u I J Bashir, Chandra S Kankipati, Sarah Jones, Robert M Newman, Stephen T Safrany, Christopher J Perry, Iain D Nicholl
Epidemiological studies indicate that long‑term aspirin usage reduces the incidence of colorectal cancer (CRC) and may protect against other non‑CRC associated adenocarcinomas, including oesophageal cancer. A number of hypotheses have been proposed with respect to the molecular action of aspirin and other non‑steroidal anti‑inflammatory drugs in cancer development. The mechanism by which aspirin exhibits toxicity to CRC has been previously investigated by synthesising novel analogues and derivatives of aspirin in an effort to identify functionally significant moieties...
January 29, 2019: International Journal of Oncology
E O Kuzichkina, O N Shilova, S M Deyev
The protein photosensitizer miniSOG is a promising agent for photodynamic therapy. The genetically encoded phototoxins 4D5scFv-miniSOG and DARPin-miniSOG specifically bind to the HER2 receptor overexpressed on the surface of cancer cells and promote receptor-mediated internalization of HER2. We show that ingestion of proteins in a complex with the receptor reduces the fluorescent signal of the phototoxic module in endosomes. In order to clarify the mechanism of decrease in the fluorescence intensity of miniSOG-based proteins as they enter a cancer cell during internalization, we analyzed the influence of different factors, including low pH, proteolysis, cofactor reduction, and shielding, on changes in the fluorescence of photosensitizers...
October 2018: Acta Naturae
Yao Luo, Yuping Han, Xingjie Hu, Min Yin, Changfeng Wu, Qian Li, Nan Chen, Yun Zhao
OBJECTIVES: Nanocarriers can greatly enhance the cellular uptake of therapeutic agents to regulate cell proliferation and metabolism. Nevertheless, further application of nanocarriers is often limited by insufficient understanding of the mechanisms of their uptake and intracellular behaviour. MATERIALS AND METHODS: Fluorescent polymer dots (Pdots) are coated with synthetic octaarginine peptides (R8) and are analysed for cellular uptake and intracellular transportation in HeLa cervical cancer cells via single particle tracking...
February 1, 2019: Cell Proliferation
Elisabetta Vulpis, Alessandra Soriani, Cristina Cerboni, Angela Santoni, Alessandra Zingoni
Natural killer (NK) cells are innate lymphoid cells that play a pivotal role in tumor surveillance. Exosomes are nanovesicles released into the extracellular environment via the endosomal vesicle pathway and represent an important mode of intercellular communication. The ability of anticancer chemotherapy to enhance the immunogenic potential of malignant cells mainly relies on the establishment of the immunogenic cell death (ICD) and the release of damage-associated molecular patterns (DAMPs). Moreover, the activation of the DNA damage response (DDR) and the induction of senescence represent two crucial modalities aimed at promoting the clearance of drug-treated tumor cells by NK cells...
January 31, 2019: International Journal of Molecular Sciences
Caroline Ladurantie, Mathilde Coustets, Georges Czaplicki, Pascal Demange, Serge Mazères, Stéphanie Dauvillier, Justin Teissié, Marie-Pierre Rols, Alain Milon, Vincent Ecochard, Grégori Gross, Laurent Paquereau
The development of drug delivery and imaging tools is a major challenge in human health, in particular in cancer pathologies. This work describes the optimization of a protein nanocontainer, belonging to the lectin protein family, for its use in epithelial cancer diagnosis and treatment. Indeed, it specifically targets a glycosidic marker, the T antigen, which is known to be characteristic of epithelial cancers. Its quaternary structure reveals a large hydrated inner cavity able to transport small therapeutic molecules...
February 1, 2019: Nanoscale
Mark F McCarty, Simon Iloki-Assanga, Lidianys Maria Lewis Lujan, James J DiNicolantonio
Receptor-mediated activation of NADPH oxidase complexes commonly occurs in endosomes; the hydrogen peroxide produced by the dismutation of superoxide generated within the endosomes often functions to boost receptor function by reversibly inhibiting protein tyrosine phosphatases or by promoting formation of signaling complexes. NADPH oxidase-mediated formation of superoxide entails transfer of two electrons (provided by NADPH) from the cytosol to the endosomal lumen, where two molecules of superoxide are generated...
February 2019: Medical Hypotheses
Hyuk Lee, Hongsuk Park, Hyeong Sup Yu, Kun Na, Kyung Taek Oh, Eun Seong Lee
Immunotherapy can potentially treat cancers on a patient-dependent manner. Most of the efforts expended on anticancer vaccination parallel the efforts expended on prototypical immunization in infectious diseases. In this study, we designed and synthesized pH-responsive extracellular vesicles (EVs) coupled with hyaluronic acid (HA), 3-(diethylamino)propylamine (DEAP), monophosphoryl lipid A (MPLA), and mucin 1 peptide (MUC1), referred to as HDEA@EVAT. HDEA@EVAT potentiated the differentiation and maturation of monocytes into dendritic cells (DCs) and the priming of CD8⁺ T-cells for cancer therapy...
January 27, 2019: Pharmaceutics
Sharleen V Menezes, Zaklina Kovacevic, Des R Richardson
The metastasis suppressor, N-Myc downstream-regulated gene-1 (NDRG1) inhibits a plethora of oncogenic signaling pathways by down-regulating the epidermal growth factor receptor (EGFR). Herein, we examined the mechanism involved in NDRG1-mediated EGFR down-regulation. NDRG1 over-expression potently increased the levels of mitogen-inducible gene 6 (MIG6), which inhibits EGFR and facilitates its lysosomal processing and degradation. Conversely, silencing NDRG1 in multiple human cancer cell-types decreased MIG6 expression, demonstrating the regulatory role of NDRG1...
January 24, 2019: Journal of Biological Chemistry
Muye He, Lei Huang, Xinyu Hou, Chen Zhong, Zaina Ait Bachir, Minbo Lan, Rongjun Chen, Feng Gao
Cancer immunotherapy is considered to be one of the alternatives to traditional chemotherapy. It's known that foreign antigen, such as ovalbumin (OVA), can label tumor cells, leading to neoantigen recognition by cytotoxic T lymphocytes. Herein, a novel multifunctional micelle coated with PEGylated hyaluronic acid (HA) was prepared through self-assembly and electrostatic interaction. The OVA-loaded micelle with uniform size (132.1 ± 0.2 nm in diameter) exhibited favorable stability and sustained release profiles...
January 21, 2019: International Journal of Pharmaceutics
Rapeepat Sangsuwan, Phum Tachachartvanich, Matthew B Francis
Protein-based drugs are a promising class of therapeutics, but poor membrane permeability typically limits their application to extracellular receptors. Delivery strategies that can transport functional proteins to reach intracellular targets are needed, but with many current approaches, biomolecules become entrapped in the endosomes. This greatly reduces the effective concentrations of therapeutic agents at the target sites. Herein, we report a bioconjugation-based approach for intracellular protein delivery by site-selectively attaching amphiphilic polymers to the N-terminal positions of proteins using 2-pyridinecarboxaldehyde groups...
January 21, 2019: Journal of the American Chemical Society
Motomu Shimaoka, Eiji Kawamoto, Arong Gaowa, Takayuki Okamoto, Eun Jeong Park
Connexins and integrins, the two structurally and functionally distinct families of transmembrane proteins, have been shown to be inter-connected by various modes of cross-talk in cells, such as direct physical coupling via lateral contact, indirect physical coupling via actin and actin-binding proteins, and functional coupling via signaling cascades. This connexin-integrin cross-talk exemplifies a biologically important collaboration between channels and adhesion receptors in cells. Exosomes are biological lipid-bilayer nanoparticles secreted from virtually all cells via endosomal pathways into the extracellular space, thereby mediating intercellular communications across a broad range of health and diseases, including cancer progression and metastasis, infection and inflammation, and metabolic deregulation...
January 17, 2019: Cancers
Zehui Li, Nneka E Mbah, Jean H Overmeyer, Jeffrey G Sarver, Sage George, Christopher J Trabbic, Paul W Erhardt, William A Maltese
BACKGROUND: Synthetic indolyl- pyridinyl- propenones (IPPs) induce methuosis, a form of non-apoptotic cell death, in glioblastoma and other cancer cell lines. Methuosis is characterized by accumulation of cytoplasmic vacuoles derived from macropinosomes and late endosomes, followed by metabolic failure and rupture of the plasma membrane. However, not all IPPs that cause vacuolization are cytotoxic. The main goals of the present study were to identify key signaling pathways that contribute to methuosis induced by cytotoxic IPPs and to evaluate the anti-tumor potential of a prototype IPP in vivo...
January 16, 2019: BMC Cancer
Nadja Groysbeck, Audrey Stoessel, Mariel Donzeau, Elisabete Cruz da Silva, Maxime Lehmann, Jean-Marc Strub, Sarah Cianferani, Kassiogé Dembélé, Guy Zuber
Therapeutic monoclonal antibodies benefit to patients and the conjugation to gold nanoparticles (AuNPs) might bring additional activities to these macromolecules. However, the behavior of the conjugate will largely depend on the bulkiness of the AuNP and small sizes are moreover preferable for diffusion. Water-soluble thiolate-protected AuNPs having diameters of 2 to 3 nm can be synthesized with narrow polydispersity and can selectively react with incoming organic thiols via a SN2-like mechanism. We therefore synthesized a mixed thionitrobenzoic acid-, thioaminobenzoic acid- monolayered AuNP of 2...
January 16, 2019: Nanotechnology
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