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https://www.readbyqxmd.com/read/28812388/silk-nanoparticles-proof-of-lysosomotropic-anticancer-drug-delivery-at-single-cell-resolution
#1
John D Totten, Thidarat Wongpinyochit, F Philipp Seib
Silk nanoparticles are expected to improve chemotherapeutic drug targeting to solid tumours by exploiting tumour pathophysiology, modifying the cellular pharmacokinetics of the payload and ultimately resulting in trafficking to lysosomes and triggering drug release. However, experimental proof for lysosomotropic drug delivery by silk nanoparticles in live cells is lacking and the importance of lysosomal pH and enzymes controlling drug release is currently unknown. Here, we demonstrate, in live single human breast cancer cells, the role of the lysosomal environment in determining silk nanoparticle-mediated drug release...
August 16, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28812246/dna-tetrahedron-delivery-enhances-doxorubicin-induced-apoptosis-of-ht-29-colon-cancer-cells
#2
Guiyu Zhang, Zhiyong Zhang, Junen Yang
As a nano-sized drug carrier with the advantage of modifiability and proper biocompatibility, DNA tetrahedron (DNA tetra) delivery is hopeful to enhance the inhibitory efficiency of nontargeted anticancer drugs. In this investigation, doxorubicin (Dox) was assembled to a folic acid-modified DNA tetra via click chemistry to prepare a targeted antitumor agent. Cellular uptake efficiency was measured via fluorescent imaging. Cytotoxicity, inhibition efficiency, and corresponding mechanism on colon cancer cell line HT-29 were evaluated by MTT assay, cell proliferation curve, western blot, and flow cytometry...
August 15, 2017: Nanoscale Research Letters
https://www.readbyqxmd.com/read/28811469/rgd-delivery-of-truncated-coagulase-to-tumor-vasculature-affords-local-thrombotic-activity-to-induce-infarction-of-tumors-in-mice
#3
Rana Jahanban-Esfahlan, Khaled Seidi, Hassan Monhemi, Amir Daei Farshchi Adli, Babak Minofar, Peyman Zare, Davoud Farajzadeh, Safar Farajnia, Ramezan Behzadi, Mehran Mesgari Abbasi, Nosratollah Zarghami, Tahereh Javaheri
Induction of thrombosis in tumor vasculature represents an appealing strategy for combating cancer. Herein, we combined unique intrinsic coagulation properties of staphylocoagulase with new acquired functional potentials introduced by genetic engineering, to generate a novel bi-functional fusion protein consisting of truncated coagulase (tCoa) bearing an RGD motif on its C-terminus for cancer therapy. We demonstrated that free coagulase failed to elicit any significant thrombotic activity. Conversely, RGD delivery of coagulase retained coagulase activity and afforded favorable interaction of fusion proteins with prothrombin and αvβ3 endothelial cell receptors, as verified by in silico, in vitro, and in vivo experiments...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811347/tifa-signaling-in-gastric-epithelial-cells-initiates-the-cag-type-4-secretion-system-dependent-innate-immune-response-to-helicobacter-pylori-infection
#4
Alevtina Gall, Ryan G Gaudet, Scott D Gray-Owen, Nina R Salama
Helicobacter pylori is a bacterial pathogen that colonizes the human stomach, causing inflammation which, in some cases, leads to gastric ulcers and cancer. The clinical outcome of infection depends on a complex interplay of bacterial, host genetic, and environmental factors. Although H. pylori is recognized by both the innate and adaptive immune systems, this rarely results in bacterial clearance. Gastric epithelial cells are the first line of defense against H. pylori and alert the immune system to bacterial presence...
August 15, 2017: MBio
https://www.readbyqxmd.com/read/28811015/multiple-targeted-graphene-based-nanocarrier-for-intracellular-imaging-of-mrnas
#5
Ying Wang, Zhaohui Li, Misha Liu, Jinjin Xu, Dehong Hu, Yuehe Lin, Jinghong Li
Simultaneous detection and imaging of multiple intracellular messenger RNA (mRNAs) hold great significant for early cancer diagnostics and preventive medicine development. Herein, we propose a multiple-targeted graphene oxide (GO) nanocarrier that can simultaneously detect and image different type mRNAs in living cells. First of all, in vitro detection of multiple targets have been realized successfully based on the multiple-targeted GO nanocarrier with linear relationship ranging from 3 nM to 200 nM, as well as sensitive detection limit of 1...
August 29, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/28810897/cost-of-hospitalization-for-childbirth-in-india-how-equitable-it-is-in-the-post-nrhm-era
#6
Jaya Prasad Tripathy, Hemant D Shewade, Sanskruti Mishra, A M V Kumar, A D Harries
BACKGROUND AND OBJECTIVE: Information on out-of-pocket (OOP) expenditure during childbirth in public and private health facilities in India is needed to make rational decisions for improving affordability to maternal care services. We undertook this study to evaluate the OOP expenditure due to hospitalization from childbirth and its impact on households. METHODS: This is a secondary data analysis of a nationwide household survey by the National Sample Survey Organization in 2014...
August 15, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/28810881/comparison-of-photon-volumetric-modulated-arc-therapy-intensity-modulated-proton-therapy-and-intensity-modulated-carbon-ion-therapy-for-delivery-of-hypo-fractionated-thoracic-radiotherapy
#7
Alexander Chi, Lien-Chun Lin, Sijin Wen, Haijuan Yan, Wen-Chien Hsi
PURPOSE: The aim of the present study was to compare the dose distribution generated from photon volumetric modulated arc therapy (VMAT), intensity modulated proton therapy (IMPT), and intensity modulated carbon ion therapy (IMCIT) in the delivery of hypo-fractionated thoracic radiotherapy. METHODS AND MATERIALS: Ten selected patients who underwent thoracic particle therapy between 2015 and 2016 were re-planned to receive a relative biological effectiveness (RBE) weighted dose of 60 Gy (i...
August 15, 2017: Radiation Oncology
https://www.readbyqxmd.com/read/28810808/advances-and-challenges-in-cardiovascular-gene-therapy
#8
Seppo Ylä-Herttuala, Johanna Lähteenvuo
25 years of gene therapy have not yet yielded standard therapeutic solutions for clinical use in cardiovascular medicine, but several therapeutic targets have been identified and foundations for future therapies have been set. The safety of viral gene therapy has been established with a wide variety of vectors and transgenes. Adenoviruses and adeno-associated viruses have established their role as vectors of choice for many cardiovascular applications and appropriate viral doses have been established for several tissues and applications...
August 16, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28810532/plga-ctab-curcumin-nanoparticles-fabrication-characterization-and-molecular-basis-of-anticancer-activity-in-triple-negative-breast-cancer-cell-lines-mda-mb-231-cells
#9
Ramovatar Meena, Sumit Kumar, Raj Kumar, Usha Singh Gaharwar, Paulraj Rajamani
Triple-negative breast cancers (TNBC) are aggressive cancers, which do not control by hormonal therapy or therapies that target HER-2 receptors. Curcumin (Cur) has shown cytotoxic effects in multiple cancer cell lines. However, its medical uses remain limited due to low aqueous solubility and poor bioavailability. Therefore, present study was aimed to fabricate the small positive charge curcumin nanoparticles (CN) by nanoprecipitation methods using PLGA and CTAB, and to evaluate its anticancer efficacy and underlying the mechanism in triple negative breast cancer cell lines (MDA-MB-231 cells)...
August 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28810244/increasing-haemodialytic-clearances-as-residual-renal-function-declines-an-incremental-approach
#10
Kamonwan Tangvoraphonkchai, Andrew Davenport
Many patients with chronic kidney disease start undergoing thrice-weekly haemodialysis (HD), aiming for an HD sessional dialyzer urea clearance target, irrespective of whether they have residual renal function (RRF). While increasing sessional dialyzer urea clearance above a target of 1.2 has not been shown to improve patient survival, it has been shown that the preservation of RRF improves patient self-reported outcomes and survival. Observational studies have suggested that initiating twice-weekly HD schedules leads to greater preservation of RRF...
August 16, 2017: Blood Purification
https://www.readbyqxmd.com/read/28810183/computer-modeling-of-drug-delivery-in-the-anterior-human-eye-after-subconjunctival-and-episcleral-implantation
#11
Feng Zhang, Han Chen, Yukan Huang
Recently, subconjunctival and episcleral implants have been proposed in the treatment of anterior eye diseases. In order to improve the delivery efficacy, it is important to understand the transport process of the implanted drugs. A 3D computational model, which includes heat transfer, aqueous humor (AH) flow, as well as diffusive and convective transport of the drug concentration, is developed to study the temporal and spatial evolution of the drug in the anterior segment of a human eye after subconjunctival and episcleral implantation, with a focus on drug delivery to three targets: iris, lens, and trabecular meshwork (TM)...
July 31, 2017: Computers in Biology and Medicine
https://www.readbyqxmd.com/read/28809970/ph-sensitive-metal-free-carbon-monoxide-prodrugs-with-tunable-and-predictable-release-rates
#12
Xingyue Ji, Ladie Kimberly C De La Cruz, Zhixiang Pan, Vayou Chittavong, Binghe Wang
Carbon monoxide prodrugs with triggered release profiles are highly desirable for targeted CO delivery to minimize their untoward side-effects. Herein, we describe a series of pH-sensitive metal-free CO prodrugs which are stable under acidic conditions and yet begin to release CO in response to increases in pH with tunable and predictable release rates.
August 15, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28809766/crispr-cas9-editing-of-nf1-gene-identifies-crmp2-as-a-therapeutic-target-in-neurofibromatosis-type-1-related-pain-that-is-reversed-by-s-lacosamide
#13
Aubin Moutal, Xiaofang Yang, Wennan Li, Kerry B Gilbraith, Shizhen Luo, Song Cai, Liberty François-Moutal, Lindsey A Chew, Seul Ki Yeon, Shreya S Bellampalli, Chaoling Qu, Jennifer Y Xie, Mohab M Ibrahim, May Khanna, Ki Duk Park, Frank Porreca, Rajesh Khanna
Neurofibromatosis type 1 (NF1) is a rare autosomal dominant disease linked to mutations of the Nf1 gene. Patients with NF1 commonly experience severe pain. Studies on mice with Nf1 haploinsufficiency have been instructive in identifying sensitization of ion channels as a possible cause underlying the heightened pain suffered by patients with NF1. However, behavioral assessments of Nf1 mice have led to uncertain conclusions about the potential causal role of Nf1 in pain. We used the clustered regularly interspaced short palindromic repeats (CRISPR)-associated 9 (CRISPR/Cas9) genome editing system to create and mechanistically characterize a novel rat model of NF1-related pain...
July 3, 2017: Pain
https://www.readbyqxmd.com/read/28809479/natural-seminal-amyloids-as-targets-for-development-of-synthetic-inhibitors-of-hiv-transmission
#14
Daniel A Sheik, Stephen Dewhurst, Jerry Yang
Amyloids refer to a class of protein or peptide aggregates that are heterogeneous in size, morphology, and composition, and are implicated to play a central role in many neurodegenerative and systemic diseases. The strong correlation between biological activity and extent of aggregation of amyloidogenic proteins and peptides has led to an explosion of research efforts to target these materials with synthetic molecules or engineered antibodies to try to attenuate their function in disease pathology. Although many of these efforts to attenuate amyloid function have shown great promise in laboratory settings, the vast majority of work has been focused on targeting amyloids associated with neurologic diseases, which has been met with significant additional challenges that preclude clinical evaluation...
August 15, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28809432/intranasal-administration-of-brain-targeted-hp-%C3%AE-cd-chitosan-nanoparticles-for-delivery-of-scutellarin-a-compound-with-protective-effect-in-cerebral-ischaemia
#15
Shanshan Liu, Paul C Ho
OBJECTIVES: Scutellarin (SCU) is a traditional Chinese medicine used for the treatment of ischaemic cerebrovascular disease, but its clinic applications have been limited due to its poor water solubility, poor bioavailability and short half-life. In comparison with the conventional oral and intravenous administration, nasal administration may help targeting the drug more directly to brain. Thus, we proposed to employ a novel SCU-loaded HP-β-CD/chitosan nanoparticles (CD/CS-SCU-NPs) to deliver SCU to brain through the nasal route...
August 15, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28809111/tumor-acidic-microenvironment-targeted-drug-delivery-based-on-phlip-modified-mesoporous-organosilica-nanoparticles
#16
Yunlei Zhang, Meng Dang, Ying Tian, Yefei Zhu, Wenfei Liu, Wei Tian, Yunyan Su, Qianqian Ni, Chaoli Xu, Nan Lu, Jun Tao, Yanjun Li, Shuang Zhao, Ying Zhao, Zhenlu Yang, Li Sun, Zhaogang Teng, Guangming Lu
Enhancing the tumor-targeting delivery of chemotherapeutic drugs is important yet challenging for improving therapeutic efficacy and reducing the side effects. Here, we firstly construct a drug delivery system for targeting tumor acidic microenvironment by modification of pH (low) insertion peptide (pHLIP) on mesoporous organosilica nanoparticles (MONs). The MONs has thioether-bridged framework, uniform diameter (60 nm), good biocompatibility and high doxorubicin (DOX) loading capacity (334 mg/g). The DOX loaded in the pHLIP modified MONs can be released responsive to glutathione and low pH circumstance, ensuring the chemotherapeutic drug exerts higher cytotoxic effects to cancer cells than normal cells because of high intracellular GSH of tumor cells and low pH of tumor microenvironment...
August 15, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28809092/particle-targeting-in-complex-biological-media
#17
REVIEW
Qiong Dai, Nadja Bertleff-Zieschang, Julia A Braunger, Mattias Björnmalm, Christina Cortez-Jugo, Frank Caruso
Over the past few decades, nanoengineered particles have gained increasing interest for applications in the biomedical realm, including diagnosis, imaging, and therapy. When functionalized with targeting ligands, these particles have the potential to interact with specific cells and tissues, and accumulate at desired target sites, reducing side effects and improve overall efficacy in applications such as vaccination and drug delivery. However, when targeted particles enter a complex biological environment, the adsorption of biomolecules and the formation of a surface coating (e...
August 15, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28808971/high-throughput-screening-for-identification-of-novel-innate-immune-activators
#18
Bryan J Gall, Victor R DeFilippis
Modern drug discovery has embraced in vitro platforms that enable investigation of large numbers of compounds within tractable timeframes and for feasible costs. These endeavors have been greatly aided in recent years by advances in molecular and cell-based methods such as gene delivery and editing technology, advanced imaging, robotics, and quantitative analysis. As such, the examination of phenotypic impacts of novel molecules may only be limited by the size of the compound collection. Innate immune signaling processes in mammalian cells are especially amenable to high-throughput screening platforms since the cellular responses elicited by their activation often result in high level transcription that can be harnessed in the form of bioluminescent or fluorescent signal...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28808837/a-multiparticulate-delivery-system-for-potential-colonic-targeting-using-bovine-serum-albumin-as-a-model-protein
#19
Bowen Jiang, Hua Yu, Yongrong Zhang, Hanping Feng, Stephen W Hoag
PURPOSE: There are many important diseases whose treatment could be improved by delivering a therapeutic protein to the colon, for example, Clostridium difficile infection, ulcerative colitis and Crohn's Disease. The goal of this project was to investigate the feasibility of colonic delivery of proteins using multiparticulate beads. METHODS: In this work, bovine serum albumin (BSA) was adopted as a model protein. BSA was spray layered onto beads, followed by coating of an enteric polymer EUDRAGIT® FS 30 D to develop a colonic delivery system...
August 14, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28808212/recent-advances-in-arsenic-trioxide-encapsulated-nanoparticles-as-drug-delivery-agents-to-solid-cancers
#20
Anam Akhtar, Scarlet Xiaoyan Wang, Lucy Ghali, Celia Bell, Xuesong Wen
Since arsenic trioxide was first approved as the front line therapy for acute promyelocytic leukemia 25 years ago, its anti-cancer properties for various malignancies have been under intense investigation. However, the clinical successes of arsenic trioxide in treating hematological cancers have not been translated to solid cancers. This is due to arsenic's rapid clearance by the body's immune system before reaching the tumor site. Several attempts have henceforth been made to increase its bioavailability toward solid cancers without increasing its dosage albeit without much success...
January 19, 2017: Journal of Biomedical Research
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