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D P N Gonçalves, D M Park, T L Schmidt, C Werner
Glioblastoma multiforme (GBM) contains a population of tumor initiating stem-like cells, termed cancer stem cells (CSCs). These CSCs, which are resistant to chemo- and radiotherapy, are thought to persist after treatment and drive tumor recurrence. Thus, it is believed that the elimination of CSCs can lead to GBM remission. GBM CSCs express Nestin on their surface, and can be therefore targeted via this protein. Gold nanorods (AuNRs) functionalized with an engineered, modular peptide that recognizes Nestin (NesPEG-AuNRs) were used to target the models of solid tumors originated from human GBM CSC multicellular tumor spheroids (MCTS)...
March 20, 2018: Biomaterials Science
Kai Huang, Chuan Fang, Kaikai Yi, Xing Liu, Hongzhao Qi, Yanli Tan, Junhu Zhou, Ying Li, Mingyang Liu, Yuqing Zhang, Jingxuan Yang, Jianning Zhang, Min Li, Chunsheng Kang
Exosomes play critical roles in intercellular communication in both nearby and distant cells in individuals and organs. Polymerase I and transcript release factor (PTRF), also known as Cavin1, has previously been described as a critical factor in caveola formation, and aberrant PTRF expression has been reported in various malignancies. However, the function of PTRF in tumor progression remains controversial, and its role in glioma is poorly understood. In this study, we report that PTRF is associated with malignancy grade and poor prognosis in glioma patients...
2018: Theranostics
De-Gang Ji, Yan Zhang, Song-Mei Yao, Xu-Jie Zhai, Li-Rong Zhang, Yao-Zhong Zhang, Hui Li
Caveolin-1 (Cav-1), as a membrane protein involved in the formation of caveolae, binds steroid receptors and endothelial nitric oxide synthase, limiting its translocation and activation. In the present study, we investigated the role of Cav-1 in the progression of hepatic fibrosis induced by carbon tetrachloride (CCl4 ) in murine animals. Therefore, the wild type (WT) and Cav-1-knockout (Cav-1-/- ) mice were used in our study and subjected to CCl4 . The results indicated that CCl4 induced the decrease of Cav-1 expression in liver tissue samples...
March 14, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Guanyu Chen, Darren Svirskis, Weiyue Lu, Man Ying, Yuan Huang, Jingyuan Wen
Gemcitabine is a nucleoside analogue effective against a number of cancers. However, the full potential of this drug has not been realised, in part due to low oral bioavailability and frequent dosing requirements. This study reports the synthesis, in-vitro, ex-vivo and in-vivo evaluation of trimethyl chitosan (TMC) - CSKSSDYQC (CSK) peptide conjugates capable of enhancing the oral bioavailability of gemcitabine due to the ability to target intestinal goblet cells and promote intestinal cellular uptake. TMC was synthesized by a novel two-step methylation method to improve quanternization and yield...
March 13, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Bin Li, Xiao-Xue Zhang, Hao-Yan Huang, Li-Qing Chen, Jing-Hao Cui, Yanli Liu, Hehua Jin, Beom-Jin Lee, Qing-Ri Cao
This study aims to construct and evaluate RGD-decorated chitosan (CS)-functionalized pH-responsive single-walled carbon nanotube (SWCNT) carriers using docetaxel (DTX) as a model anticancer drug. DTX was loaded onto SWCNT via π-π stacking interaction (SWCNT-DTX), followed by the non-covalent conjugation of RGD-decorated CS to SWCNT-DTX to prepare RGD-CS-SWCNT-DTX. The RGD-CS-SWCNT-DTX showed significantly higher drug release than the pure drug, giving higher release rate at pH5.0 (68%) than pH7.4 (49%). The RGD-CS-SWCNT-DTX could significantly inhibit the growth of A549 tumor cells in vitro, and the uptake amount of A549 cells was obviously higher than that of MCF-7 cells...
March 10, 2018: International Journal of Pharmaceutics
Zahra Tahmasebi Fard, Nahid Nafisi
BACKGROUND: Caveolae play a role in cell signal transduction, kinetic regulation of transport vesicles, and cellular physiology. In this study, we evaluated the role of caveolin-1 (CAV-1) genotypes in the risk of breast cancer. PATIENTS AND METHODS: We evaluated 6 single nucleotide polymorphisms of the CAV-1 gene in a sample size of 406 participants. Six polymorphisms-G32124A (rs3807992), T29107A (rs7804372), T28608A (rs3757733), G21985A (rs12672038), G14713A (rs3807987), and C521A (rs1997623)-were assessed using restriction fragment length polymorphism polymerase chain reaction...
January 31, 2018: Clinical Breast Cancer
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
Jing Sun, Chong Qiu, Yiping Diao, Wei Wei, Hongwei Jin, Yi Zheng, Jiancheng Wang, Lihe Zhang, Zhenjun Yang
Small interfering RNA (siRNA) has been continuously explored for clinical applications. However, neither nanocarriers nor conjugates have been able to remove the obstacles. In this study, we employed a combined nanochemistry strategy to optimize its delivery dilemma, where different interactions and assembly modes were cooperatively introduced into the forming process of siRNA/lipids nanoplexes. In the nanoplexes, the 3',3″-bis-peptide-siRNA conjugate (pp-siRNA) and gemini-like cationic lipids (CLDs) were employed as dual regulators to improve their bio-behavior...
March 2, 2018: Molecular Therapy. Nucleic Acids
Bappa Maiti, Mohini Kamra, Anjali A Karande, Santanu Bhattacharya
Herein, five new α-tocopheryl cationic gemini lipids with hydroxyethyl bearing headgroups (THnS, n = 4, 5, 6, 8, 12) have been synthesized for efficient plasmid DNA (pDNA) delivery into cancer cells. Among these gemini lipid formulations, the lipid with an octamethylene [-(CH2 )8 ] spacer (TH8S) showed the highest transfection efficiency (TE) that was comparable to that of the commercial standard lipofectamine 2000 (L2K) in terms of luciferase expression in HepG2 (liver hepatocellular carcinoma) cells. The addition of the helper lipid DOPE (1,2-dioleoyl phosphatidyl ethanolamine) with cationic lipids in mixed liposomes further enhanced the TE and the optimized molar ratio was 2 : 1 (DOPE : cationic lipid)...
March 2, 2018: Organic & Biomolecular Chemistry
Bo Yang, Xuefeng Qi, Hui Guo, Peilong Jia, Shuying Chen, Zhijie Chen, Ting Wang, Jingyu Wang, Qinghong Xue
Peste des petits ruminants virus (PPRV) causes an acute and highly contagious disease of sheep and goats and has spread with alarming speed around the world. The pathology of Peste des petits ruminants is linked to retrogressive changes and necrotic lesions in lymphoid tissues and epithelial cells. However, the process of PPRV entry into host epithelial cells remains largely unknown. Here, we performed a comprehensive study of the entry mechanism of PPRV into caprine endometrial epithelial cells (EECs). We clearly demonstrated that PPRV internalization was inhibited by chloroquine and ammonium chloride, which elevate the pH of various organelles...
2018: Frontiers in Microbiology
Yukinobu Kodama, Waka Nishigaki, Tadahiro Nakamura, Shintaro Fumoto, Koyo Nishida, Tomoaki Kurosaki, Hiroo Nakagawa, Takashi Kitahara, Takahiro Muro, Hitoshi Sasaki
We developed and optimized a novel gene delivery vector constructed electrostatically with an anionic biological component and a cationic biological component. Cationic binary complexes of plasmid DNA (pDNA) with novo-protamine sulfate as a medical product (PRT complexes) demonstrated high gene expression with minimal cytotoxicity, likely related with its total cationic charge. Subsequently, anionic compounds were added to the PRT complexes to form ternary complexes with neutral or anionic charges. Among the anionic compounds examined, chondroitin sulfate sodium (CS) as a medical product encapsulated the PRT complexes to produce stable ternary complexes (CS complexes) at charge ratios of ≥4 with pDNA...
2018: Biological & Pharmaceutical Bulletin
Isabel Abánades Lázaro, Sandra Abánades Lázaro, Ross S Forgan
Dual delivery of dichloroacetate and 5-fluorouracil from Zr MOFs into cancer cells is found to enhance in vitro cytotoxicity. Tuning particle size and, more significantly, surface chemistry, further improves cytotoxicity by promoting caveolae-mediated endocytosis and cytosolic cargo delivery.
February 27, 2018: Chemical Communications: Chem Comm
Elda E Sánchez, Roschman González, Sara Lucena, Stefanie García, Héctor J Finol, Montamas Suntravat, María E Girón, Irma Fernández, Alexis Rodríguez-Acosta
Crotamine is a cationic, non-enzymatic, protein integrating a minor family of myotoxins, composed of 42 amino acid residues, described in Viperidae and Crotalidae snake's families that has been used in neuroscience research, drug progressing and molecular diversity reports. Crotamine-like protein (CLP) from C.o.helleri venom was isolated in fraction 5 from 7 peaks obtained by sulfopropyl waters protein pak cationic exchange column. In tricine-SDS-PAGE under non-reduced conditions this CLP showed a single band of ~8 kDa molecular weight...
March 2018: Ultrastructural Pathology
Shengnan Xiang, Melika Sarem, Samveg Shah, V Prasad Shastri
Nanomedicines can be taken up by cells via nonspecific and dynamin-dependent (energy-dependent) clathrin and caveolae-mediated endocytosis. While significant effort has focused on targeting pathway-specific transporters, the role of nanobiophysics in the cell lipid bilayer nanoparticle uptake pathway remains largely unexplored. In this study, it is demonstrated that stiffness of lipid bilayer is a key determinant of uptake of liposomes by mammalian cells. Dynamin-mediated endocytosis (DME) of liposomes is found to correlate with its phase behavior, with transition toward solid phase promoting DME, and transition toward fluidic phase resulting in dynamin-independent endocytosis...
February 20, 2018: Small
Stella M Lu, Gregory D Fairn
The plasma membrane is compartmentalized into several distinct regions or domains, which show a broad diversity in both size and lifetime. The segregation of lipids and membrane proteins is thought to be driven by the lipid composition itself, lipid-protein interactions and diffusional barriers. With regards to the lipid composition, the immiscibility of certain classes of lipids underlies the "lipid raft" concept of plasmalemmal compartmentalization. Historically, lipid rafts have been described as cholesterol and (glyco)sphingolipid-rich regions of the plasma membrane that exist as a liquid-ordered phase that are resistant to extraction with non-ionic detergents...
February 18, 2018: Critical Reviews in Biochemistry and Molecular Biology
Gina J Fiala, Susana Minguet
T and B lymphocytes are key players of the adaptive immune system. They recognize pathogenic cues via the T cell antigen receptor (TCR) and the B cell antigen receptor (BCR) to get activated and execute their protective function. TCR and BCR signaling are initiated at the plasma membrane and subsequently propagated into the cell, ultimately leading to cell activation and a protective immune response. However, inappropriate activation of T and B cells can be detrimental to the host resulting in autoimmune disorders, immunodeficiencies, and cancer...
2018: Advances in Immunology
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
Sumei Zhang, Rui Shi, Shaolong Chen, Xiang Wei, Qing Zhou, Yuan Wang
Caveolin-1 is a scaffold protein of caveolae in the mucosa of the gastrointestinal tract and acts as a tumor modulator by interacting with cell adhesion molecules and signaling receptors. Caveolin-1 stabilizes cell-cell and cell-matrix contacts and is a hallmark of a number of different types of human cancer, including gastric cancer. All-trans retinoic acid (ATRA), a derivative of vitamin A, has been demonstrated to exhibit tumor inhibitory effects in acute leukemia and certain types of solid tumor. In the present study, treatment with ATRA was demonstrated to inhibit the proliferation of gastric cancer cell line SGC7901, in a time- and dose-dependent manner...
February 2018: Oncology Letters
M Varela-Guruceaga, F I Milagro, J A Martínez, C de Miguel
Obesity is characterized by hypertrophy and hyperplasia of adipose tissue, which have been related to the development of hypoxia and insulin resistance. On the other hand, caveolin-1 (Cav-1), one of the main proteins of caveolae, promotes insulin receptor (IR) phosphorylation and the subsequent activation of insulin signaling. In this work we investigated the effect of hypoxia on Cav-1 regulation and the status of insulin signaling in 3T3-L1 adipocytes. Our results showed that hypoxia inhibited adipogenesis and insulin signaling in adipocytes...
January 30, 2018: Molecular and Cellular Endocrinology
Xianbing Zhu, Xiaoyuan Ji, Na Kong, Yunhan Chen, Morteza Mahmoudi, Xiaoding Xu, Li Ding, Wei Tao, Ting Cai, Yujing Li, Tian Gan, Austin Barrett, Zameer Bharwani, Hongbo Chen, Omid C Farokhzad
Emerging two-dimensional (2D) nanomaterials, such as transition-metal dichalcogenides (TMDs) nanosheets (NSs), have shown tremendous potential for use in a wide variety of fields including cancer nanomedicine. The interaction of nanomaterials with biosystems is of critical importance for their safe and efficient application. However, a cellular-level understanding of the nano-bio interactions of these emerging 2D nanomaterials (i.e., intracellular mechanisms) remains elusive. Here we chose molybdenum disulfide (MoS2) NSs as representative 2D nanomaterials to gain a better understanding of their intracellular mechanisms of action in cancer cells, which play a significant role in both their fate and efficacy...
February 6, 2018: ACS Nano
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