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https://www.readbyqxmd.com/read/28641400/cytosolic-delivery-of-sirna-by-ultra-high-affinity-dsrna-binding-proteins
#1
Nicole J Yang, Monique J Kauke, Fangdi Sun, Lucy F Yang, Katie F Maass, Michael W Traxlmayr, Yao Yu, Yingda Xu, Robert S Langer, Daniel G Anderson, K Dane Wittrup
Protein-based methods of siRNA delivery are capable of uniquely specific targeting, but are limited by technical challenges such as low potency or poor biophysical properties. Here, we engineered a series of ultra-high affinity siRNA binders based on the viral protein p19 and developed them into siRNA carriers targeted to the epidermal growth factor receptor (EGFR). Combined in trans with a previously described endosome-disrupting agent composed of the pore-forming protein Perfringolysin O (PFO), potent silencing was achieved in vitro with no detectable cytotoxicity...
June 21, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28641106/antisense-oligonucleotides-translation-from-mouse-models-to-human-neurodegenerative-diseases
#2
REVIEW
Kathleen M Schoch, Timothy M Miller
Multiple neurodegenerative diseases are characterized by single-protein dysfunction and aggregation. Treatment strategies for these diseases have often targeted downstream pathways to ameliorate consequences of protein dysfunction; however, targeting the source of that dysfunction, the affected protein itself, seems most judicious to achieve a highly effective therapeutic outcome. Antisense oligonucleotides (ASOs) are small sequences of DNA able to target RNA transcripts, resulting in reduced or modified protein expression...
June 21, 2017: Neuron
https://www.readbyqxmd.com/read/28640900/predictors-of-exclusive-breastfeeding-and-consumption-of-soft-semi-solid-or-solid-food-among-infants-in-boucle-du-mouhoun-burkina-faso-a-cross-sectional-survey
#3
Jenny A Cresswell, Rasmané Ganaba, Sophie Sarrassat, Simon Cousens, Henri Somé, Abdoulaye Hama Diallo, Veronique Filippi
INTRODUCTION: Exclusive breastfeeding is among the most effective interventions for preventing child mortality. The objectives of this paper are to describe infant feeding knowledge and practices in Boucle du Mouhoun, Burkina Faso; to identify predictors of exclusive breastfeeding among infants <6 months, and consumption of soft, semi-solid or solid food among infants 6-11 months; to describe mothers' sources of information regarding breastfeeding. METHODS: A cross-sectional survey (n = 2288) of a representative sample of women aged 15-49 years with at least one live birth in past year took place during June and July 2015...
2017: PloS One
https://www.readbyqxmd.com/read/28640891/baculoviral-delivery-of-crispr-cas9-facilitates-efficient-genome-editing-in-human-cells
#4
Sanne Hindriksen, Arne J Bramer, My Anh Truong, Martijn J M Vromans, Jasmin B Post, Ingrid Verlaan-Klink, Hugo J Snippert, Susanne M A Lens, Michael A Hadders
The CRISPR/Cas9 system is a highly effective tool for genome editing. Key to robust genome editing is the efficient delivery of the CRISPR/Cas9 machinery. Viral delivery systems are efficient vehicles for the transduction of foreign genes but commonly used viral vectors suffer from a limited capacity in the genetic information they can carry. Baculovirus however is capable of carrying large exogenous DNA fragments. Here we investigate the use of baculoviral vectors as a delivery vehicle for CRISPR/Cas9 based genome-editing tools...
2017: PloS One
https://www.readbyqxmd.com/read/28640703/integrating-evidence-based-medicine-for-treatment-of-spinal-metastases-into-a-decision-framework-neurologic-oncologic-mechanicals-stability-and-systemic-disease
#5
Ori Barzilai, Ilya Laufer, Yoshiya Yamada, Daniel S Higginson, Adam M Schmitt, Eric Lis, Mark H Bilsky
Patients with cancer are frequently affected by spinal metastases. Treatment is palliative, with the principle goals of pain relief, preservation of neurologic function, and improvement in quality of life. In the past decade, we have witnessed a dramatic change in the treatment paradigms due to the development of improved surgical strategies and systemic and radiation therapy. The most important change to these paradigms has been the integration of spinal stereotactic radiosurgery (SSRS), allowing delivery of tumoricidal radiation doses with sparing of nearby organs at risk...
June 22, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28640590/chlorin-e6-functionalized-theranostic-multistage-nanovectors-transported-by-stem-cells-for-effective-photodynamic-therapy
#6
Simo Näkki, Jonathan Martinez, Michael Evangelopoulos, Wujun Xu, Vesa-Pekka Lehto, Ennio Tasciotti
Approaches to achieve site-specific and targeted delivery that provide an effective solution to reduce negative, off target side-effects are urgently needed for cancer therapy. Here, we utilized a Trojan horse-like strategy to carry photosensitizer Chlorin e6 conjugated porous silicon multistage nanovectors with tumor homing mesenchymal stem cells for targeted photodynamic therapy and diagnosis. The inherent versatility of multistage nanovectors permitted the conjugation of photosensitizers to enable precise cell death induction (60%) upon photodynamic therapy, while simultaneously retaining the loading capacity to load various payloads, such as antitumor drugs and diagnostic nanoparticles...
June 22, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28640587/silica-nanoparticle-as-a-lymph-node-targeting-platform-for-vaccine-delivery
#7
Myunggi An, Meng Li, Jingchao Xi, Haipeng Liu
Nanoparticles have emerged as the platform of choice to improve the efficacy and safety of subunit vaccines. A major challenge underlying the use of nanomaterials in vaccines lies in the particle designs that can efficiently target and activate the antigen-presenting cells, especially dendritic cells. Here we show a toll-like receptor 9 (TLR-9) agonist and antigen co-loaded, silica nanoparticles (SiNPs) are able to accumulate in antigen presenting cells in the draining lymph nodes after injection. Vaccine loaded SiNPs led to dramatically enhanced induction of antigen-specific B and T cell responses as compared to soluble vaccines, which in turn drove a protective antitumoral immunity in a murine tumor model...
June 22, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28637126/ecological-momentary-assessment-for-rehabilitation-of-chronic-illness-and-disability
#8
Ashlee McKeon, Michael McCue, Elizabeth Skidmore, Michelle Schein, Jamie Kulzer
PURPOSE: The main objectives of this manuscript were to provide a theoretical perspective on naturalistic delivery in rehabilitation based upon a literature review and establish a rationale for using ecological momentary assessment (EMA) for naturalistic assessment for chronic illness and disability (CID) in rehabilitation. METHOD: Existing literature on EMA use across CID cohorts was gathered and analyzed to form a theoretical overview of implementation of this method in research...
February 7, 2017: Disability and Rehabilitation
https://www.readbyqxmd.com/read/28637023/cationic-liquid-crystalline-nanoparticles-for-the-delivery-of-synthetic-rnai-based-therapeutics
#9
Emanuela Gentile, Taro Oba, Jing Lin, Ruping Shao, Feng Meng, Xiaobo Cao, Heather Y Lin, Majidi Mourad, Apar Pataer, Veerabhadran Baladandayuthapani, Dong Cai, Jack A Roth, Lin Ji
RNA interference (RNAi)-based therapeutics have been used to silence the expression of targeted pathological genes. Small interfering RNA (siRNAs) and microRNA (miRNAs) inhibitor have performed this function. However, short half-life, poor cellular uptake, and nonspecific distribution of small RNAs call for the development of novel delivery systems to facilitate the use of RNAi. We developed a novel cationic liquid crystalline nanoparticle (CLCN) to efficiently deliver synthetic siRNAs and miRNAs. CLCNs were prepared by using high-speed homogenization and assembled with synthetic siRNA or miRNA molecules in nuclease-free water to create CLCN/siRNA or miRNA complexes...
June 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636973/amide-to-triazole-switch-vs-in-vivo-nep-inhibition-approaches-to-promote-radiopeptide-targeting-of-grpr-positive-tumors
#10
Theodosia Maina, Aikaterini Kaloudi, Ibai E Valverde, Thomas L Mindt, Berthold A Nock
INTRODUCTION: Radiolabeled bombesin (BBN)-analogs have been proposed for diagnosis and therapy of gastrin-releasing peptide receptor (GRPR)-expressing tumors, such as prostate, breast and lung cancer. Metabolic stability represents a crucial factor for the success of this approach by ensuring sufficient delivery of circulating radioligand to tumor sites. The amide-to-triazole switch on the backbone of DOTA-PEG4-[Nle(14)]BBN(7-14) (1) was reported to improve the in vitro stability of resulting (177)Lu-radioligands...
June 10, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/28636956/elicitation-of-robust-tier-2-neutralizing-antibody-responses-in-nonhuman-primates-by-hiv-envelope-trimer-immunization-using-optimized-approaches
#11
Matthias Pauthner, Colin Havenar-Daughton, Devin Sok, Joseph P Nkolola, Raiza Bastidas, Archana V Boopathy, Diane G Carnathan, Abishek Chandrashekar, Kimberly M Cirelli, Christopher A Cottrell, Alexey M Eroshkin, Javier Guenaga, Kirti Kaushik, Daniel W Kulp, Jinyan Liu, Laura E McCoy, Aaron L Oom, Gabriel Ozorowski, Kai W Post, Shailendra K Sharma, Jon M Steichen, Steven W de Taeye, Talar Tokatlian, Alba Torrents de la Peña, Salvatore T Butera, Celia C LaBranche, David C Montefiori, Guido Silvestri, Ian A Wilson, Darrell J Irvine, Rogier W Sanders, William R Schief, Andrew B Ward, Richard T Wyatt, Dan H Barouch, Shane Crotty, Dennis R Burton
The development of stabilized recombinant HIV envelope trimers that mimic the virion surface molecule has increased enthusiasm for a neutralizing antibody (nAb)-based HIV vaccine. However, there is limited experience with recombinant trimers as immunogens in nonhuman primates, which are typically used as a model for humans. Here, we tested multiple immunogens and immunization strategies head-to-head to determine their impact on the quantity, quality, and kinetics of autologous tier 2 nAb development. A bilateral, adjuvanted, subcutaneous immunization protocol induced reproducible tier 2 nAb responses after only two immunizations 8 weeks apart, and these were further enhanced by a third immunization with BG505 SOSIP trimer...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28636640/targeted-nanodiamonds-for-identification-of-subcellular-protein-assemblies-in-mammalian-cells
#12
Michael P Lake, Louis-S Bouchard
Transmission electron microscopy (TEM) can be used to successfully determine the structures of proteins. However, such studies are typically done ex situ after extraction of the protein from the cellular environment. Here we describe an application for nanodiamonds as targeted intensity contrast labels in biological TEM, using the nuclear pore complex (NPC) as a model macroassembly. We demonstrate that delivery of antibody-conjugated nanodiamonds to live mammalian cells using maltotriose-conjugated polypropylenimine dendrimers results in efficient localization of nanodiamonds to the intended cellular target...
2017: PloS One
https://www.readbyqxmd.com/read/28636400/click-biotinylation-of-plga-template-for-biotin-receptor-oriented-delivery-of-doxorubicin-hydrochloride-in-4t1-cell-induced-breast-cancer
#13
Yuvraj Singh, K K Durga Rao Viswanadham, Arun Kumar Jajoriya, Jayagopal Meher, Kavit Raval, Swati Jaiswal, Jayant Dewangan, H K Bora, Srikanta Kumar Rath, Jawahar Lal, Durga Prasad Mishra, Manish Kumar Chourasia
PLGA was functionalized with PEG and biotin using click chemistry to generate a biotin receptor targeted copolymer (Biotinylated-PEG-PLGA) which in turn was used to fabricate ultrafine nanoparticles (BPNP) of doxorubicin hydrochloride (DOX) for effective delivery in 4T1 cell induced breast cancer. However adequate entrapment of a hydrophilic bioactive like DOX in a hydrophobic polymer system made of PLGA is not usually possible. We therefore modified a conventional W/O/W emulsion method by utilizing ammonium chloride in the external phase to constrain DOX in dissolved polymer phase by supressing its inherent aqueous solubility as per common ion effect...
June 21, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28636389/tumor-microenvironment-responsive-multistaged-nanoplatform-for-systemic-rnai-and-cancer-therapy
#14
Xiaoding Xu, Phei Er Saw, Wei Tao, Yujing Li, Xiaoyuan Ji, Mikyung Yu, Morteza Mahmoudi, Jonathan Rasmussen, Dana Ayyash, Yuxiao Zhou, Omid C Farokhzad, Jinjun Shi
While RNA interference (RNAi) therapy has demonstrated significant potential for cancer treatment, effective and safe systemic delivery of RNAi agents such as small interfering RNA (siRNA) into tumor cells in vivo remains challenging. We herein reported a unique multistaged siRNA delivery nanoparticle (NP) platform, which is comprised of (i) a polyethylene glycol (PEG) surface shell, (ii) a sharp tumor microenvironment (TME) pH-responsive polymer that forms the NP core, and (iii) charge-mediated complexes of siRNA and tumor cell-targeting- and penetrating-peptide-amphiphile (TCPA) that are encapsulated in the NP core...
June 21, 2017: Nano Letters
https://www.readbyqxmd.com/read/28636088/multicompartment-drug-release-system-for-dynamic-modulation-of-tissue-responses
#15
Aaron H Morris, Rajwant S Mahal, Jillian Udell, Michelle Wu, Themis R Kyriakides
Pharmacological modulation of responses to injury is complicated by the need to deliver multiple drugs with spatiotemporal resolution. Here, a novel controlled delivery system containing three separate compartments with each releasing its contents over different timescales is fabricated. Core-shell electrospun fibers create two of the compartments in the system, while electrosprayed spheres create the third. Utility is demonstrated by targeting the foreign body response to implants because it is a dynamic process resulting in implant failure...
June 21, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28635614/advanced-treatment-planning-using-direct-4d-optimisation-for-pencil-beam-scanned-particle-therapy
#16
Kinga Bernatowicz, Ye Zhang, Rosalind Lucy Perrin, Damien Charles Weber, Antony John Lomax
We report on development of a new four-dimensional (4D) optimisation approach for scanned proton beams, which incorporates both irregular motion patterns and the delivery dynamics of the treatment machine into the plan optimiser. Furthermore, we assess the effectiveness of this technique to reduce dose to critical structures in proximity to moving targets, while maintaining effective target dose homogeneity and coverage. The proposed approach has been tested using both a simulated phantom and a clinical liver cancer case, and allows for realistic 4D calculations and optimisation using irregular breathing patterns extracted from e...
June 21, 2017: Physics in Medicine and Biology
https://www.readbyqxmd.com/read/28635550/peptide-grafted-and-self-assembled-poly-%C3%AE-glutamic-acid-phenylalanine-nanoparticles-targeting-camptothecin-to-glioma
#17
Hitesh Kulhari, Srinivasa R Telukutla, Deep Pooja, Ravi Shukla, Ramakrishna Sistla, Vipul Bansal, David J Adams
AIM: To synthesize cRGDfK peptide conjugated poly(γ-glutamic acid)-phenylalanine nanoparticles to improve the therapeutic efficacy of camptothecin (CPT) against glioblastoma multiforme. METHODS: Peptide-conjugated, drug-loaded nanoparticles (cRGDfK-conjugated camptothecin-loaded PGA-PA nanoparticles [RCPN]) were prepared and physico-chemically characterized using different techniques. Nanoparticles were evaluated for in vitro anticancer activity, cellular uptake, induction of apoptosis and wound healing cell migration against U87MG human glioblastoma cells...
June 21, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28635366/redox-biology-of-leishmania-and-macrophage-targeted-nanoparticles-for-therapy
#18
Hafiz Shoaib Sarwar, Sohail Akhtar, Muhammad Farhan Sohail, Zaeema Naveed, Muhammad Rafay, Akhtar Nadhman, Masoom Yasinzai, Gul Shahnaz
Intramacrophage parasite 'Leishmania' has developed various mechanisms for proficient uptake into macrophages and phagosome regulation to avoid macrophage's oxidative burst induced by peroxide, hydroxyl radical, hypochlorous acid and peroxynitrite production. One major barrier for impairing the accession of old fashioned anti-Leishmanial drugs is intrinsic incapability to pass through cell membranes and limiting their abilities to ultimately destroy intracellular pathogens. Receptor-mediated targeted drug delivery to the macrophages by using nanoparticles emerges as promising strategy to improve therapeutic efficacy of old-fashioned drug...
June 21, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28635335/a-novel-synergetic-targeting-strategy-for-glioma-therapy-employing-borneol-combination-with-angiopep-2-modified-dox-loaded-pamam-dendrimer
#19
Shunping Han, Hongyue Zheng, Yanping Lu, Yue Sun, Anhao Huang, Weidong Fei, Xiaowei Shi, Xiuling Xu, Jingjing Li, Fanzhu Li
Glioma is the most common primary malignant brain tumor and the effect of chemotherapy is hampered by low permeability across the blood-brain-barrier (BBB). Borneol is a time-honored 'Guide' drug in traditional Chinese medicine and has been proved to be capable of promoting free drugs into the brain efficiently, but there are still risks that free drugs, especially anti-glioma drugs, may be disassembled and metabolized before penetrating the BBB and caused the whole brain distribution. The purpose of this paper was to investigate whether borneol intervention could facilitate the BBB penetration and assist glioma treatment by combining with doxorubicin (DOX) loaded PAMAM dendrimers drug delivery system modified with Angiopep-2 (a ligand of the low-density lipoprotein receptor-related protein, which overexpress both in the BBB and gliomas)...
June 21, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28635259/a-delivery-system-targeting-haemagglutinin-of-influenza-virus-a-to-facilitate-antisense-based-anti-h1n1-therapy
#20
Xiaoran Ding, Jing Yang, Dandan Lu, Qingjun Li, Zhaoyan Zhang, Zhe Zhou, Shengqi Wang
Antisense oligonucleotides (ODNs) are therapeutic molecules that hybridize to complementary target mRNA sequences. To further overcome the poor cellular uptake of ODNs, we proposed a novel strategy to deliver ODNs by conjugating the anti-influenza A virus (IAV) ODN with a peptide showing high affinity to the haemagglutinin (HA) on the surface of IAV particles or the IAV infected host cells. The HA-specific binding peptides were selected by phage display and the individual binding clones are characterized by DNA sequencing, and the selected phage was further assayed by ELISA...
June 21, 2017: Bioconjugate Chemistry
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