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Optimization of Micromagnetic Separation for Bacteremia Treatment 微磁分离处理菌血症的工艺优化
RAN
Pub Date : 2017-12-01 DOI: 10.11159/ijtan.2017.004
Stephen Neil Petty Valenzuela, Sinead E Miller, Charleson S. Bell, T. Giorgio
Bacteremia and related syndromes such as sepsis and septic shock are becoming an increasing health concern due in large part to the rise of antibiotic resistance and unmet challenges for rapid diagnosis. Extracorporeal bacterial separation methods are currently under development to identify pathogens and reduce bacterial load. Previous studies have generated models to understand the progression of bacteremia. Here, a physiologically-based pharmacokinetic model was integrated with a physically-based magnetic separation model to inform the design of a micromagnetic separation device. This modeling demonstrates that smallfootprint microfluidic devices are not efficient enough for bacteremia treatment in large living systems and further research into high-throughput extracorporeal blood-cleansing devices is required.
菌血症和相关综合征,如败血症和感染性休克,正在成为日益严重的健康问题,这在很大程度上是由于抗生素耐药性的上升和快速诊断方面未遇到的挑战。体外细菌分离方法目前正在开发中,以识别病原体和减少细菌负荷。以前的研究已经建立了模型来了解菌血症的进展。本研究将基于生理的药代动力学模型与基于物理的磁分离模型相结合,为微磁分离装置的设计提供信息。该模型表明,小尺寸的微流体装置对于大型生命系统中的菌血症治疗不够有效,需要进一步研究高通量体外血液净化装置。
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引用次数: 1
Management Innovation in Nanotechnology Sector: The First Insights in México 纳米技术领域的管理创新:在msamxico的第一个见解
RAN
Pub Date : 2017-04-01 DOI: 10.11159/ICNNFC17.115
Juan Mejía-Trejo, Zaira Yunuen Garcia-Carvaja, Gilberto Israel González-Ordaz
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引用次数: 2
A Reprogrammable Universal Logic Gate Based on a Nano Cantilever Resonator 基于纳米悬臂谐振器的可编程通用逻辑门
RAN
Pub Date : 2017-04-01 DOI: 10.11159/icnnfc17.101
Karumbaiah N. Chappanda, S. Ilyas, S. Kazmi, J. Holguin, P. Costa, M. Younis
K. N. Chappanda, S. Ilyas, S. N. R. Kazmi, J. Holguin, P. M. F. J. Costa and M. I. Younis Nano/Micro Mechanics and Motion Laboratory Laboratory for Carbon Nanostructures Physical Science and Engineering Division, King Abdullah University of Science and Technology Thuwal, 23955-6900, Kingdom of Saudi Arabia jorge.holguinlerma@kaust.edu.sa; pedro.dacosta@kaust.edu.sa; karumbaiah.nanaiah@kaust.edu.sa saad.ilyas@kaust.edu.sa; syed.kazmi@kaust.edu.sa; mohammad.younis@kaust.edu.sa
K. N. Chappanda, S. Ilyas, S. N. R. Kazmi, J. Holguin, P. M. F. J. Costa和M. I. Younis纳米/微力学与运动实验室碳纳米结构物理科学与工程系实验室,沙特阿拉伯王国图沃尔,23955-6900 jorge.holguinlerma@kaust.edu.sa;pedro.dacosta@kaust.edu.sa;karumbaiah.nanaiah@kaust.edu.sa saad.ilyas@kaust.edu.sa;syed.kazmi@kaust.edu.sa;mohammad.younis@kaust.edu.sa
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引用次数: 0
Structure-Function Correlation in Novel Nanomedicines for RNA Delivery 新型RNA递送纳米药物的结构-功能相关性研究
RAN
Pub Date : 2017-04-01 DOI: 10.11159/NDDTE17.118
Sara S. Nogueira, J. Moreno, H. Haas, K. Reuter, Stephanie Erbar, Peter Languth
Extended Abstract Messenger RNA (mRNA)-based nanomedicines constitute a new class of pharmaceutical products, with a variety of potential applications, ranging from tumour immunotherapy to protein substitution. For patient administration, mRNA can be formulated in different types of nanoparticle vehicles, in order to protect the mRNA from degradation and facilitate uptake resulting in expression at the target site. BioNTech has brought the first intravenously injectable mRNA nanoparticle product for cancer immunotherapy into clinical trials, which consist of a lipoplex formulation obtainable from cationic liposomes [1, 2]. Lipid nanoparticles (LNPs) are another type of delivery vehicle and have been successfully used in the past, for example, to deliver siRNA to the liver [3]. Recently, LNPs have been also been used as carriers for mRNA, for induction potent CD8 T cell immune response [4], showing that LNPs can be versatile delivery systems for RNA in diverse therapeutic settings. Typically, LNPs are comprised of an ionizable lipid, one or several helper lipids and a polyethylene glycol (PEG). The ionizable lipid, which is positively charged at low pH and neutral at high pH, is selected to allow high RNA encapsulation and efficacy and to facilitate endosomal escape. The activity of the mRNA LNP formulations strongly depends on the type of ionisable lipid, on the lipid composition, the lipid to RNA ratio, and several other molecular and structural parameters. Furthermore, the activity may vary also for different application routes (e.g., intravenous, intramuscular, subcutaneous), or if therapeutic approaches are intended. So far, there is no clear common understanding on the correlation between the molecular parameters of the LNPs and the biological activity. Therefore, in our study we have systematically studied certain molecular and formulation parameters of mRNA loaded LNPs, in order to correlate them with the biological function. In particular we have thoroughly investigated physicochemical characteristics (internal organization, fluidity, size) and the structure of the LNPs (in particular by small angle x-ray scattering) and determined the biological activity in vitro and in vivo. The structural and functional coherencies in the LNPs were compared in those of lipoplexes, and the effects of selected lipids were highlighted. Such understanding of the molecular basis of delivery complexes will help to identify criteria for the development of improved mRNA delivery vehicles for clinical development.
基于信使RNA (mRNA)的纳米药物构成了一类新的药物产品,具有多种潜在的应用,从肿瘤免疫治疗到蛋白质替代。对于患者给药,mRNA可以在不同类型的纳米颗粒载体中配制,以保护mRNA免受降解并促进摄取,从而在靶部位表达。BioNTech已经将首个用于癌症免疫治疗的静脉注射mRNA纳米颗粒产品带入临床试验,该产品由阳离子脂质体制成的脂质体组成[1,2]。脂质纳米颗粒(LNPs)是另一种类型的递送载体,在过去已被成功使用,例如,将siRNA递送到肝脏。最近,LNPs也被用作mRNA的载体,用于诱导有效的CD8 T细胞免疫反应[4],这表明LNPs可以在不同的治疗环境中作为RNA的通用递送系统。LNPs通常由一种可电离脂质、一种或几种辅助脂质和聚乙二醇(PEG)组成。选择在低pH值下带正电而在高pH值下带中性电的可电离脂质,以实现高RNA包封和效率,并促进内体逃逸。mRNA LNP制剂的活性在很大程度上取决于可电离脂质的类型、脂质的组成、脂质与RNA的比例以及其他一些分子和结构参数。此外,活性也可能因不同的应用途径(例如,静脉注射、肌肉注射、皮下注射)或治疗途径而变化。到目前为止,LNPs的分子参数与生物活性之间的关系还没有明确的共识。因此,在我们的研究中,我们系统地研究了mRNA负载LNPs的某些分子和配方参数,以便将它们与生物学功能联系起来。特别是,我们深入研究了LNPs的物理化学特性(内部组织,流动性,大小)和结构(特别是通过小角度x射线散射),并确定了体外和体内的生物活性。比较了脂丛中LNPs的结构和功能一致性,并重点介绍了所选脂质的作用。这种对递送复合物分子基础的理解将有助于确定用于临床开发的改进mRNA递送载体的开发标准。
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引用次数: 0
Considerable Anti-tumour Effect of Nanoparticle-Bound Doxorubicin against 4T1 Metastatic Breast Cancer in Mice 纳米颗粒结合阿霉素对小鼠4T1转移性乳腺癌的显著抗肿瘤作用
RAN
Pub Date : 2017-04-01 DOI: 10.11159/nddte17.108
Yu. A. Malinovskaya, S. Gelperina, O. Maksimenko, V. Baklaushev
Yulia Malinovskaya, Svetlana Gelperina, Olga Maksimenko, Vladimir Baklaushev R-Pharm Drugs Technology Ltd. Khimki, Moscow Region, 141400, Russia Serbsky State Scientific Center for Social and Forensic Psychiatry Moscow, 117418, Russia j.malinowskaya@gmail.com Extended Abstract Introduction: Our previous results demonstrated a considerable antitumor effect of doxorubicin loaded in PLGA nanoparticles (Dox-PLGA NPs) coated with poloxamer 188 (P188) against the intracranial 101.8 glioblastoma in rats [1,2]. As a high-grade breast cancer is a common cause of brain metastases occurring in at least 10-16% patients [3] and doxorubicin is widely used against breast cancer, the aim of the present study was to evaluate the efficiency of Dox-PLGA NPs against 4T1 metastatic breast cancer in Balb/c mice. Methods: Dox-PLGA NPs were prepared by a double emulsion solvent evaporation technique. Chemotherapy: 4T1 murine breast cancer cells were previously modified by firefly luciferase gene transfection (4Т1-Luc2) and inoculated intracardially (1  10) into the cavity of a left ventricle of female Balb/c mice. On days 7, 10, 13, 16, and 19 after intracardial injection the tumor-bearing animals received i.v. the following formulations in the dose of 2 mg/kg (as doxorubicin): 1) Doxorubicin solution (Dox-sol), 2) Dox-PLGA NPs in PBS (DOX-PLGA), 3) Dox-PLGA NPs coated with 1% poloxamer 188 (Dox-PLGA/P188). For coating the NPs were resuspended in 1% P188 30 min before injection. Animals treated with 1% P188 solution and untreated group were used as controls 1 and 2, respectively. Organ bioluminescence intensity was assessed using an intravital fluorescence imaging system Ivis Spectrum CT on days 14 and 28 after tumor inoculation. Additionally, the presence of metastases in surviving animals was confirmed by MRI on days 21 and 28. Results: The average particle diameter was 120-130 nm, and the drug loading was 84%. The mean survival time of tumour-bearing mice was increased by >40% after treatment with Dox-PLGA NPs, as compared to control (23 days versus 15-16 days, respectively). As shown by intravital fluorescence imaging, the improved survival in the nanoparticle-treated groups also correlated with significantly lower fluorescence intensity of metastases as compared to the group treated with Dox-sol and control groups. The difference between the groups treated with DOX-PLGA and Dox-PLGA/P188 was not significant; however, in the animals treated with P188-coated NPs a somewhat lower bioluminescence of metastases was observed. Importantly, administration of nanoparticulate formulations was associated with a significantly improved tolerance of chemotherapy, as compared to free doxorubicin. Conclusion: Binding of doxorubicin to PLGA nanoparticles considerably enhanced its antitumour efficacy against 4T1 metastatic breast cancer in mice providing more pronounced inhibition of metastatic spread and higher increase of animal life-span, as compared to the free drug. Moreover,
Yulia Malinovskaya, Svetlana Gelperina, Olga Maksimenko, Vladimir Baklaushev R-Pharm药物技术有限公司摘要简介:我们之前的研究结果表明,载多柔比星的PLGA纳米颗粒(Dox-PLGA NPs)包被波洛沙姆188 (P188),对大鼠颅内101.8胶质母细胞瘤有相当大的抗肿瘤作用[1,2]。由于高级别乳腺癌是至少10-16%患者发生脑转移的常见原因,而阿霉素被广泛用于治疗乳腺癌,本研究的目的是评估Dox-PLGA NPs对Balb/c小鼠4T1转移性乳腺癌的疗效。方法:采用双乳液溶剂蒸发法制备Dox-PLGA NPs。化疗:先前通过萤火虫荧光素酶基因转染(4Т1-Luc2)修饰4T1小鼠乳腺癌细胞,并将其接种于雌性Balb/c小鼠左心室腔内(110)。在心内注射后第7、10、13、16、19天,荷瘤动物静脉注射剂量为2mg /kg(阿霉素)的制剂:1)阿霉素溶液(Dox-sol), 2) PBS中的Dox-PLGA NPs (Dox-PLGA), 3) 1% poloxam188包被的Dox-PLGA NPs (Dox-PLGA/P188)。在注射前30分钟将NPs用1% P188重悬。1% P188溶液处理组和未处理组分别作为对照1和对照2。肿瘤接种后第14天和第28天,使用活体荧光成像系统Ivis光谱CT评估器官生物发光强度。此外,存活动物在第21天和第28天通过MRI证实了转移的存在。结果:平均粒径为120 ~ 130 nm,载药量为84%。与对照组相比,Dox-PLGA NPs治疗后,荷瘤小鼠的平均生存时间增加了40%(分别为23天和15-16天)。活体荧光成像显示,与Dox-sol治疗组和对照组相比,纳米颗粒治疗组的生存率提高也与转移瘤的荧光强度显著降低相关。DOX-PLGA组与DOX-PLGA /P188组间差异无统计学意义;然而,在用p188包被的NPs处理的动物中,转移灶的生物发光程度有所降低。重要的是,与游离的阿霉素相比,纳米颗粒制剂的施用与化疗耐受性的显着改善有关。结论:与游离药物相比,多柔比星与PLGA纳米颗粒结合可显著增强其对小鼠4T1转移性乳腺癌的抗肿瘤作用,更明显地抑制转移扩散,延长动物寿命。此外,Dox-PLGA NPs似乎毒性较低,这很可能是由于它们改变了生物分布模式。
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引用次数: 0
The Effect of Silver Nanoparticles on the Scavenger Receptor-Scara1 on Microglia 纳米银对小胶质细胞清道夫受体scara1的影响
RAN
Pub Date : 2017-04-01 DOI: 10.11159/icnb17.115
Sikorska Katarzyna, Grądzka Iwona, Wasyk Iwona
Extended Abstract Alzheimer's disease is one of the most prevalent neurodegenerative diseases in the world. The neuropathological hallmark of Alzheimer's disease is extracellular deposit of amyloid-β (Aβ) in the brain. Microglial cells are able to remove of Aβ aggregates by receptor-dependent endocytosis [1,3]. Nanotechnology is one of the fastest developing science discipline and nanoparticles (NPs), due to their strong absorption properties are widely used in industry, and also in medical diagnosis and treatment. It was documented that NPs can prevent the formation of Aß-aggregates whereby reducing their neurotoxicity and likely can impact on the Aß-uptake by microglia [2,4-7]. It is supposed that NPs can increase number of emerging phagocytosis bubbles and the Aβ uptake due to the co-transport phenomenon, or in contrary reduce the number of lipid rafts available and therefore inhibit of Aβ transport by some kind of competition. Moreover, by activating different paths to cell signaling, NPs can probably change the expression of the amyloid β-receptors on microglia cell membranes. The goal of our study was to verify whether silver nanoparticles (AgNPs, 20 nm, BSA coated) can change the ability of microglial scavenger receptor 1 (Scara1) for the Aß (1-42) uptake and influence gene or protein expression of these receptors in mouse BV-2 cells. The results from flow cytometry indicate that both Aβ and AgNPs are taken up by microglial cells using the same receptor: AgNPs (50 μg/ml) can decrease the uptake of Aβ by about 80% compared to the control group and Scara1 inhibitor (poliinosinic acid) diminish both AgNPs and Aß peptide uptake. Real-time PCR analysis showed that AgNPs did not change the Scara1 gene expression. The Western blotting (measuring the whole receptor content) revealed a slight decrease in the protein receptor level after treatment of cells with AgNPs (50 μg/ml). On the other hand, the content of the receptor on the cell surface, measured cytometrically, was greatly diminished in the presence of AgNPs. In summary, AgNPs clearly blocked the receptor and so they may play rather disadvantageous role in Aβ removal. Results from the Project “The influence of nanoparticles on beta-amyloid removal by microglia cells”. From National Science Centre, Project duration: 09. 2014-09.2017 Project ID:UMO-2013/11/N/NZ7/00415.
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引用次数: 0
Green Manufacturing of Core-Shell Polyvinyl Alcohol-Gelatin Electrospun Nanofiber Scaffolds 核壳聚乙烯醇-明胶静电纺纳米纤维支架的绿色制造
RAN
Pub Date : 2017-04-01 DOI: 10.11159/icnb17.106
Mustafa Şengör, M. A. Gulgun, S. Altıntaş
Extended Abstract In tissue engineering, natural/synthetic polymer based fibrous composite scaffolds obtained via electrospinning method were shown to support the cell adhesion and tissue regeneration. However, electrospinning of natural polymers requires the use of toxic solvents that are negatively affecting the cell proliferation and biocompatibility of the produced scaffolds in addition to the usage of acidic solvents which will result in massive biodegradation inside the body[1] .Here, a method was proposed that is higher safety for the patient and even for the experimentalists who are using harmful and highly volatile solvents. Two types of polymers were used in the synthesis of the scaffolds by mimicking the key features of the tissue extracellular matrix which contains gelatin and coaxially organized nanofibers. Coaxial electrospinning technique was used to obtain core(PVA)-shell (gelatin) nanofibers. While material in the shell provides recognition sites for the tissue cells, core material provides mechanical endurance. Different from conventional methods, proposed work aims to lower the steps of application of the scaffold to the harmed tissue by using only deionized water as solvent. Instead of dissolving PVA and gelatin in toxic and acidic solvents, they were dissolved in the deionized water above the gelation temperature. Later, coaxial electrospinning generated increased cell spread and mechanical stiffness. The samples were characterized by scanning and transmission electron microscopy. Based on the experimental results it is concluded that electrospun fibers obtained from the 8% concentrated gelatin solution had a beaded structure, whereas the coaxially fabricated PVA and gelatin from the same concentration solutions did not show any beaded morphology. Also core-shell fibers have diameters down to 180 nm. This result showed that PVA aids to the uniform gelatin fiber formation which, may give higher mechanical stability. The electron microscopy analysis leading to these results has received support by the Nanotechnology Research and Application Center at Sabanci University.
在组织工程中,通过静电纺丝方法获得的天然/合成聚合物纤维复合材料支架支持细胞粘附和组织再生。然而,天然聚合物的静电纺丝需要使用有毒溶剂,这对细胞增殖和所生产的支架的生物相容性有负面影响,此外还需要使用酸性溶剂,这将导致体内大量的生物降解。在这里,我们提出了一种对患者甚至对使用有害和高挥发性溶剂的实验人员来说更安全的方法。利用两种聚合物模拟了组织细胞外基质的主要特征,即明胶和同轴组织纳米纤维。采用同轴静电纺丝技术制备了芯(PVA)-壳(明胶)纳米纤维。壳中的材料为组织细胞提供了识别位点,而芯材料提供了机械耐久性。与传统方法不同的是,本文提出的工作旨在通过仅使用去离子水作为溶剂来降低支架在损伤组织中的应用步骤。将PVA和明胶溶解在高于凝胶温度的去离子水中,而不是在有毒和酸性溶剂中溶解。后来,同轴静电纺丝增加了细胞扩散和机械刚度。用扫描电镜和透射电镜对样品进行了表征。实验结果表明,在8%浓度明胶溶液中制备的静电纺丝纤维具有珠状结构,而在相同浓度溶液中同轴制备的PVA和明胶则不具有珠状结构。此外,芯壳纤维的直径可低至180纳米。结果表明,聚乙烯醇有助于明胶纤维的均匀形成,具有较高的机械稳定性。导致这些结果的电子显微镜分析得到了萨班齐大学纳米技术研究和应用中心的支持。
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引用次数: 0
Design of TiOxNy for Developing Layered Stent Technology 开发层状支架技术的TiOxNy设计
RAN
Pub Date : 2017-04-01 DOI: 10.11159/icnnfc17.137
A. Ficai, M. Sonmez, Roxana Doina Trusc, B. Vasile, Denisa Fica, E. Andronescu
Anton Ficai, Maria Sonmez, Roxana Doina Trusca, Bogdan Stefan Vasile, Denisa Ficai, Ecaterina Andronescu Department of Science and Engineering of Oxide Materials and Nanomaterials, Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest 1-7 Gh. Polizu St., 011061-Bucharest, Romania anton.ficai@upb.ro; ficaimaria@yahoo.com National Research & Development Institute for Textiles and Leather–division: Leather and Footwear Research Institute, Bucharest, Romania
Anton Ficai, Maria Sonmez, Roxana Doina Trusca, Bogdan Stefan Vasile, Denisa Ficai, Ecaterina Andronescu,布加勒斯特理工大学应用化学与材料科学学院氧化材料与纳米材料科学与工程系波利祖街,011061-布加勒斯特,罗马尼亚anton.ficai@upb.ro;ficaimaria@yahoo.com国家纺织和皮革研究与发展研究所:皮革和鞋类研究所,布加勒斯特,罗马尼亚
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引用次数: 0
Metronomic Nanocaged Doxorubicin Prevents Chemoresistance and Cardiotoxicity in Breast Cancer 节拍器纳米包裹的阿霉素预防乳腺癌的化疗耐药和心脏毒性
RAN
Pub Date : 2017-04-01 DOI: 10.11159/NDDTE17.123
S. Mazzucchelli, Marta Truff, M. Bellini, M. Rizzuto, D. Prosperi, F. Corsi
Serena Mazzucchelli, Marta Truffi, Michela Bellini, Maria A. Rizzuto, Davide Prosperi, Fabio Corsi Department of Biomedical and Clinical Sciences, University of Milan Via G. B. Grassi 74, 20157 Milan, Italy serena.mazzucchelli@gmail.com; marta.truffi@unimi.it Surgery Department, Breast Unit, ICS Maugeri S. p. A. SB Pavia, Italy fabio.corsi@unimi.it Department of Biotechnology and Biosciences, University of MilanBicocca Piazza della Scienza 2, 20126 Milan, Italy michi.bellini@gmail.com; m.rizzuto3@campus.unimib.it; davide.prosperi@unimib.it
Serena Mazzucchelli, Marta Truffi, Michela Bellini, Maria A. Rizzuto, Davide Prosperi, Fabio Corsi米兰大学生物医学与临床科学系Via g.b. Grassi 74, 20157意大利米兰serena.mazzucchelli@gmail.com;marta.truffi@unimi.it意大利帕维亚ICS Maugeri s.p . A. SB乳房外科fabio.corsi@unimi.it米兰比可卡大学生物技术与生物科学系,20126意大利米兰michi.bellini@gmail.com;m.rizzuto3@campus.unimib.it;davide.prosperi@unimib.it
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引用次数: 0
Anti-CD19 Gold Nanostars as New Therapeutic Vectors for the Treatment of Acute Lymphoblastic Leukemia 抗cd19金纳米星作为治疗急性淋巴细胞白血病的新载体
RAN
Pub Date : 2017-04-01 DOI: 10.11159/nddte17.116
A. Tatar, T. Nagy-Simon, A. Jurj, I. Berindan‐Neagoe, C. Tomuleasa, D. Cialla‐May, S. Aștilean, S. Boca
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引用次数: 0
期刊
RAN
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