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https://www.readbyqxmd.com/read/28938600/application-of-dual-targeting-drug-delivery-system-for-the-improvement-of-anti-glioma-efficacy-of-doxorubicin
#1
Zhenliang Sun, Xuebing Yan, YiBo Liu, Linsheng Huang, Cheng Kong, Xiao Qu, Man Wang, Renyuan Gao, Huanlong Qin
Chemotherapy of glioma is always hampered by the unsatisfactory tumor accumulation of drugs, of which the most noticeable obstacle is the limited drug permeability from vessels into tumor inner. In the present study, we developed a novel nanocarrier for the delivery of doxorubicin to brain tumor. Such novel drug delivery system was mainly composed of a tumor homing peptide and DOX-loaded PLA nanoparticles (AP1-NP-DOX). CRKRLDRNC peptide, named as AP1, was a newly glioma affinity peptide which could specifically binds to interleukin-4 receptor (IL-4R), highly expressing on both glioma cells and angiogenesis...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938577/mitochondria-chaperone-grp75-moonlighting-as-a-cell-cycle-controller-to-derail-endocytosis-provides-an-opportunity-for-nanomicrosphere-intracellular-delivery
#2
Zhihui Gao, Xiuran Niu, Qing Zhang, Hang Chen, Aiai Gao, Shanshan Qi, Rong Xiang, Mattias Belting, Sihe Zhang
Understanding how cancer cells regulate endocytosis during the cell cycle could lead us to capitalize this event pharmacologically. Although certain endocytosis pathways are attenuated during mitosis, the endocytosis shift and regulation during the cell cycle have not been well clarified. The conventional concept of glucose-regulated proteins (GRPs) as protein folding chaperones was updated by discoveries that translocated GRPs assume moonlighting functions that modify the immune response, regulate viral release, and control intracellular trafficking...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938559/doxorubicin-loaded-platelets-conjugated-with-anti-cd22-mabs-a-novel-targeted-delivery-system-for-lymphoma-treatment-with-cardiopulmonary-avoidance
#3
Peipei Xu, Huaqin Zuo, Rongfu Zhou, Fan Wang, Xu Liu, Jian Ouyang, Bing Chen
B-cell lymphoma accounts for approximately 85% of all adult non-Hodgkin's lymphoma cases. Doxorubicin (DOX) is an indispensable drug for the treatment of non-Hodgkin's lymphoma. However, DOX causes severe cardiotoxicity, which limits its use in conventional treatment strategies. In this study, we developed a novel drug delivery system for lymphoma treatment: DOX-loaded platelets that were conjugated with anti-CD22 monoclonal antibodies (mAbs) (DOX-platelet-CD22). Platelets are bio- and immune-compatible drug carriers that can prolong the circulation time of drugs...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938558/human-menstrual-blood-derived-mesenchymal-stem-cells-as-a-cellular-vehicle-for-malignant-glioma-gene-therapy
#4
Xiao-Jun Wang, Bing-Yu Xiang, Ya-Hui Ding, Lu Chen, Hai Zou, Xiao-Zhou Mou, Charlie Xiang
Despite many advances in conventional treatment strategies, there is no effective treatment modality for malignant gliomas. Gene therapy may offer a promising option for gliomas and several gene therapy approaches have shown anti-tumor efficiency in previous studies. Mesenchymal stem cell-based gene therapies, in which stem cells are genetically engineered to express therapeutic molecules, have shown tremendous potential because of their innate homing ability. In this study, human menstrual blood-derived MSCs (MenSC), a novel type of multipotential MSCs displays tropism for human malignant glioma when used as a gene delivery vehicle for therapeutics...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938471/low-vitamin-b12-in-pregnancy-is-associated-with-adipose-derived-circulating-mirs-targeting-ppar%C3%AE-and-insulin-resistance
#5
Antonysunil Adaikalakoteswari, Manu Vatish, Mohammad Tauqeer Alam, Sascha Ott, Sudhesh Kumar, Ponnusamy Saravanan
Context: Low vitamin B12 (B12) during pregnancy is associated with higher maternal obesity, insulin resistance(IR) and gestational diabetes(GDM). B12 is a key co-factor in 1-carbon metabolism. Objective: We hypothesize that B12 plays a role in epigenetic regulation by altering circulating miRNAs(miRs) during adipocyte differentiation and results in an adverse metabolic phenotype. Design, settings and main-outcome measure: Human pre-adipocyte cell-line(Chub-S7) were differentiated in various B12 concentrations: Control(500nM), LowB12(0...
September 5, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28938163/tumor-cell-targeted-delivery-of-crispr-cas9-by-aptamer-functionalized-lipopolymer-for-therapeutic-genome-editing-of-vegfa-in-osteosarcoma
#6
Chao Liang, Fangfei Li, Luyao Wang, Zong-Kang Zhang, Chao Wang, Bing He, Jie Li, Zhihao Chen, Atik Badshah Shaikh, Jin Liu, Xiaohao Wu, Songlin Peng, Lei Dang, Baosheng Guo, Xiaojuan He, D W T Au, Cheng Lu, Hailong Zhu, Bao-Ting Zhang, Aiping Lu, Ge Zhang
Osteosarcoma (OS) is a highly aggressive pediatric cancer, characterized by frequent lung metastasis and pathologic bone destruction. Vascular endothelial growth factor A (VEGFA), highly expressed in OS, not only contributes to angiogenesis within the tumor microenvironment via paracrine stimulation of vascular endothelial cells, but also acts as an autocrine survival factor for tumor cell themselves, thus making it a promising therapeutic target for OS. CRISPR/Cas9 is a versatile genome editing technology and holds tremendous promise for cancer treatment...
September 13, 2017: Biomaterials
https://www.readbyqxmd.com/read/28938010/epidermal-growth-factor-receptor-targeted-sonoporation-with-microbubbles-enhances-therapeutic-efficacy-in-a-squamous-cell-carcinoma-model
#7
Fumika Hirabayashi, Kenjiro Iwanaga, Toshinori Okinaga, Osamu Takahashi, Wataru Ariyoshi, Ryo Suzuki, Mutsumi Sugii, Kazuo Maruyama, Kazuhiro Tominaga, Tatsuji Nishihara
Sonoporation is a drug and gene delivery system using ultrasonication that allows the intracellular delivery of foreign molecules that cannot enter cells under normal conditions. We previously reported that sonoporation with microbubbles (MBs) could achieve effective intracellular drug delivery to human gingival squamous carcinoma Ca9-22 cells. In this study, we developed anti-epidermal growth factor receptor (EGFR) antibody-conjugated MBs (EGFR-MBs) and evaluated their capacity to enhance anti-cancer drug toxicity in vitro and in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28937950/vectors-and-gene-delivery-to-the-retina
#8
Arthur Planul, Deniz Dalkara
One of the great advantages of the retina as a target tissue for gene delivery is the wide array of genetic tools that have been developed in the past decade. This includes a variety of vectors for therapeutic gene delivery to most types of retinal neurons and glia, as well as cell type-specific promoters for restricted gene expression in distinct neuronal subtypes. Within the scope of neuroscience applications and for gene therapy, it is now routine to express reporter genes, replacement genes, neuronal activity indicators, and microbial opsins in specific neuronal types in the mouse retina...
September 15, 2017: Annual Review of Vision Science
https://www.readbyqxmd.com/read/28937916/nanoparticles-for-advanced-photodynamic-therapy-of-cancer
#9
Heidi Abrahamse, Cherie Ann Kruger, Sania Kadanyo, Ajay Mishra
The world widespread rise in cancer incidence has caused an increase in the demand for effective and safe materials for treatment. One of the most prevalent forms of treatment for cancer is photodynamic therapy (PDT), which is seen as an alternative to radiotherapy, as well as chemotherapy. In more recent years, researchers are exploring new nanotechnology-based strategies to improve the effectiveness of PDT. OBJECTIVE: The objective of this review is to explore the current trends and research findings associated with PDT and the development of nanotechnology as treatment modality for cancer...
September 21, 2017: Photomedicine and Laser Surgery
https://www.readbyqxmd.com/read/28937754/bi-functional-elastin-like-polypeptide-nanoparticles-bind-rapamycin-and-integrins-and-suppress-tumor-growth-in-vivo
#10
Jugal P Dhandhukia, Pu Shi, Santosh Peddi, Zhe Li, Suhaas Rayudu Aluri, Yaping Ju, Dab Brill, Wan Wang, Siti Janib, Yi-An Lin, Shuanglong Liu, Honggang Cui, John Andrew MacKay
Recombinant protein-polymer scaffolds such as Elastin-Like Polypeptides (ELPs) offer drug delivery opportunities including biocompatibility, monodispersity, and multi-functionality. We recently reported that fusion of FK-506 binding protein 12 (FKBP) to an ELP nanoparticle (FSI) increases rapamycin (Rapa) solubility, suppresses growth of breast cancer xenografts, and reduces side-effects observed with free drug controls. This new report significantly advances this carrier strategy by demonstrating the co-assembly of two different ELP diblock copolymers containing drug-loading and tumor-targeting domains...
September 22, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28937621/the-development-of-a-melt-extruded-shellac-carrier-for-the-targeted-delivery-of-probiotics-to-the-colon
#11
Noel M Gately, James E Kennedy
Hot melt extrusion (HME) is considered an efficient technique in developing solid molecular dispersions, and has been demonstrated to provide sustained, modified and targeted drug delivery resulting in improved bioavailability. However, most commercial enteric or pH-responsive polymers are relatively difficult to process or have high Glass Transition Temperature (Tg) values, making their use with temperature-sensitive drugs, probiotics or biologics not viable. Shellac is a natural thermoplastic, and after a review of current literature on the pharmaceutical HME process, a possible gap in the knowledge of the use of shellac to produce dosage forms by means of HME was identified...
September 22, 2017: Pharmaceutics
https://www.readbyqxmd.com/read/28937592/spatiotemporal-control-of-doxorubicin-delivery-from-stealth-like-prodrug-micelles
#12
Li Kong, Dimitrios Poulcharidis, Gregory F Schneider, Frederick Campbell, Alexander Kros
In the treatment of cancer, targeting of anticancer drugs to the tumor microenvironment is highly desirable. Not only does this imply accurate tumor targeting but also minimal drug release en route to the tumor and maximal drug release once there. Here we describe high-loading, "stealth-like" doxorubicin micelles as a pro-drug delivery system, which upon light activation, leads to burst-like doxorbicin release. Through this approach, we show precise spatiotemporal control of doxorubicin delivery to cells in vitro...
September 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28937584/targeted-delivery-of-sirna-with-ph-responsive-hybrid-gold-nanostars-for-cancer-treatment
#13
Hongyan Zhu, Wanwan Liu, Ziting Cheng, Ke Yao, Yu Yang, Bohui Xu, Gaoxing Su
In this work, we report the engineering of gold nanostars (GNS) to deliver small interfering RNA (siRNA) into HepG2 cells. The ligand DG-PEG-Lipoic acid (LA)-Lys-9R (hydrazone) was designed to functionalize GNS, and create the nanoparticles named as 9R/DG-GNS (hydrazone). In the ligand, 2-deoxyglucose (DG) is the targeting molecule, polyethylene glycol (PEG) helps to improve the dispersity and biocompatibility, 9-poly-d-arginine (9R) is employed to provide a positive surface charge and adsorb negative siRNA, and hydrazone bonds are pH-responsive and can avoid receptor-mediated endosomal recycling...
September 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28937091/obstruction-of-braf-v600e-transcription-by-complementary-pna-oligomers-as-a-means-to-inhibit-braf-mutant-melanoma-growth
#14
J H Rothman, O Surriga, E de Stanchina, S D Vasudeva, G K Schwartz
Peptide nucleic acid (PNA) oligomers are DNA mimics, which are capable of binding gene sequences 1000-fold more avidly than complementary native DNA by strand invasion and effectively obstruct transcription. Irreversibly obstructing the transcription or replication of a gene sequence, such as BRAF(V600E), offers a potential route to specifically target the cancer cell itself. We have employed PNA oligomers to target BRAF(V600E) in a sequence-specific complementary manner. These PNAs have been modified by appending configurationally stabilizing cationic peptides in order to improve their cellular delivery and target avidity...
September 22, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/28936886/inducible-crispr-genome-editing-tool-classifications-and-future-trends
#15
Xiaofeng Dai, Xiao Chen, Qiuwu Fang, Jia Li, Zhonghu Bai
The discovery of CRISPR-Cas9/dCas9 system has reinforced our ability and revolutionized our history in genome engineering. While Cas9 and dCas9 are programed to modulate gene expression by introducing DNA breaks, blocking transcription factor recruitment or dragging functional groups towards the targeted sites, sgRNAs determine the genomic loci where the modulation occurs. The off-target problem, due to limited sgRNA specificity and genome complexity of many species, has posed concerns for the wide application of this revolutionary technique...
September 22, 2017: Critical Reviews in Biotechnology
https://www.readbyqxmd.com/read/28936747/exosomes-outlook-for-future-cell-free-cardiovascular-disease-therapy
#16
Bahar Barani, Sheeja Rajasingh, Johnson Rajasingh
Cardiovascular diseases are the number one cause of death globally with an estimated 7.4 million people dying from coronary heart disease. Studies have been conducted to identify the therapeutic utility of exosomes in many diseases, including cardiovascular diseases. It has been demonstrated that exosomes are immune modulators, can be used to treat cardiac ischemic injury, pulmonary hypertension and many other diseases, including cancers. Exosomes can be used as a biomarker for disease and cell-free drug delivery system for targeting the cells...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28936729/the-multifaceted-functions-of-exosomes-in-health-and-disease-an-overview
#17
Claudia Arenaccio, Maurizio Federico
Exosomes are extracellular vesicles of 50-150 nm in diameter secreted by basically all cell types. They mediate micro-communication among cells, tissues, and organs under both healthy and disease conditions by virtue of their ability to deliver macromolecules to target cells. Research on exosomes is a rapidly growing field, however many aspects of their biogenesis and functions still await a complete clarification. In our review we summarize most recent findings regarding biogenesis, structure, and functions of exosomes...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28936523/mesoporous-zno-nanocapsules-for-the-induction-of-enhanced-antigen-specific-immunological-responses
#18
Sumbul Afroz, Himadri Medhi, Somedutta Maity, Gillipsie Minhas, Srikanth Battu, Jeevan Giddaluru, Koushi Kumar, Pradip Paik, Nooruddin Khan
The application of nanotechnology in vaccinology has fuelled rapid advancement towards the design and development of nanovaccines. Nanoparticles have been found to enhance vaccine efficacy through the spatiotemporal orchestration of antigen delivery to secondary lymphoid organs and antigen-presentation by Antigen Presenting Cells (APCs) synchronized with stimulation of innate and adaptive immune responses. Metal based nanoparticles (MNPs) have been extensively engineered for the generation of nanovaccines owing to their intrinsic adjuvant-like properties and immunomodulatory functions...
September 22, 2017: Nanoscale
https://www.readbyqxmd.com/read/28936479/surface-coating-of-nanoparticles-reduces-background-inflammatory-activity-while-increasing-particle-uptake-and-delivery
#19
Brittany A Moser, Rachel C Steinhardt, Aaron P Esser-Kahn
In the study of host-pathogen interactions, vaccines and drug delivery, particulate delivery system are widely used to mimic pathogen size, pattern recognition receptor agonist presentation, and target cells or organs. However, some of the polymeric systems used in particulate delivery have inherent inflammatory properties that are variable and nonspecific. These properties enhance their adjuvant activity, but confound the analysis of signaling mechanisms. Here, we present a method for particle coating with minimal background immune activation via passivation of the surface with silica-silane...
February 13, 2017: ACS Biomaterials Science & Engineering
https://www.readbyqxmd.com/read/28936208/cas9-nickase-assisted-rna-repression-enables-stable-and-efficient-manipulation-of-essential-metabolic-genes-in-clostridium-cellulolyticum
#20
Tao Xu, Yongchao Li, Zhili He, Joy D Van Nostrand, Jizhong Zhou
Essential gene functions remain largely underexplored in bacteria. Clostridium cellulolyticum is a promising candidate for consolidated bioprocessing; however, its genetic manipulation to reduce the formation of less-valuable acetate is technically challenging due to the essentiality of acetate-producing genes. Here we developed a Cas9 nickase-assisted chromosome-based RNA repression to stably manipulate essential genes in C. cellulolyticum. Our plasmid-based expression of antisense RNA (asRNA) molecules targeting the phosphotransacetylase (pta) gene successfully reduced the enzymatic activity by 35% in cellobiose-grown cells, metabolically decreased the acetate titer by 15 and 52% in wildtype transformants on cellulose and xylan, respectively...
2017: Frontiers in Microbiology
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