• 【用于纳米医学和药物递送的纳米技术。】 复制标题 收藏 收藏
    DOI:10.2174/138161208785740180 复制DOI
    作者列表:Venugopal J,Prabhakaran MP,Low S,Choon AT,Zhang YZ,Deepika G,Ramakrishna S
    BACKGROUND & AIMS: :Nanotechnology is an emerging technology seeking to exploit distinct technological advances controlling the structure of materials at a reduced dimensional scale approaching individual molecules and their aggregates or supramolecular structures. The manipulation and utilization of materials at nanoscale are expected to be critical drivers of economic growth and development in this century. In recent years, nanoscale sciences and engineering have provided new avenues for engineering materials down to molecular scale precision. The resultant materials have been demonstrated to have enhanced properties and applicability; and these materials are expected to be enabling technologies in the successful development and application of nanomedicine. Nanomedicine is defined as the monitoring, repair, construction, and control of human biological systems at the molecular level using engineered nanodevices and nanostructures. Electrospinning is a simple and cost-effective technique, capable of producing continuous fibers of various materials from polymers to ceramics. The electrospinning technique is used for the preparation of nanofibers and macroporous scaffolds intended for drug delivery and tissue engineering. These have special characteristics in terms of fabrication, porosity, variable diameters, topology and mechanical properties. This review summarizes the recent developments in utilizing nanofibers for drug delivery and tissue engineering applications.
    背景与目标: : 纳米技术是一种新兴技术,旨在利用独特的技术进步来控制材料的结构,其尺寸缩小,接近单个分子及其聚集体或超分子结构。纳米级材料的操纵和利用有望成为本世纪经济增长和发展的关键动力。近年来,纳米科学和工程学为工程材料提供了新的途径,包括分子尺度的精度。所得材料已被证明具有增强的性能和适用性; 这些材料有望成为纳米医学成功开发和应用的技术。纳米医学的定义是使用工程纳米设备和纳米结构在分子水平上监测,修复,构建和控制人类生物系统。静电纺丝是一种简单且具有成本效益的技术,能够生产从聚合物到陶瓷的各种材料的连续纤维。静电纺丝技术用于制备用于药物输送和组织工程的纳米纤维和大孔支架。这些在制造,孔隙率,可变直径,拓扑结构和机械性能方面具有特殊特性。这篇综述总结了利用纳米纤维进行药物递送和组织工程应用的最新进展。
  • 【基于纳米技术的生物传感器在葡萄酒化合物分析以及葡萄酒质量和安全性控制中的应用: 重要评论。】 复制标题 收藏 收藏
    DOI:10.1080/10408398.2019.1682965 复制DOI
    作者列表:Hosnedlova B,Sochor J,Baron M,Bjørklund G,Kizek R
    BACKGROUND & AIMS: :Nanotechnology is one of the most promising future technologies for the food industry. Some of its applications have already been introduced in analytical techniques and food packaging technologies. This review summarizes existing knowledge about the implementation of nanotechnology in wine laboratory procedures. The focus is mainly on recent advancements in the design and development of nanomaterial-based sensors for wine compounds analysis and assessing wine safety. Nanotechnological approaches could be useful in the wine production process, to simplify wine analysis methods, and to improve the quality and safety of the final product.
    背景与目标: : 纳米技术是食品工业最有前途的未来技术之一。它的一些应用已经在分析技术和食品包装技术中引入。这篇综述总结了有关在葡萄酒实验室程序中实施纳米技术的现有知识。重点主要是用于葡萄酒化合物分析和评估葡萄酒安全性的基于纳米材料的传感器的设计和开发的最新进展。纳米技术方法可用于葡萄酒生产过程,简化葡萄酒分析方法,并提高最终产品的质量和安全性。
  • 【干细胞革命: 一种生物纳米技术。】 复制标题 收藏 收藏
    DOI:10.1016/j.eururo.2007.01.068 复制DOI
    作者列表:Patel HR
    BACKGROUND & AIMS: -2
    背景与目标: -2
  • 【网络和人工智能在纳米技术设计和分析中的作用。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Hudson DL,Cohen ME
    BACKGROUND & AIMS: :Techniques with their origins in artificial intelligence have had a great impact on many areas of biomedicine. Expert-based systems have been used to develop computer-assisted decision aids. Neural networks have been used extensively in disease classification and more recently in many bioinformatics applications including genomics and drug design. Network theory in general has proved useful in modeling all aspects of biomedicine from healthcare organizational structure to biochemical pathways. These methods show promise in applications involving nanotechnology both in the design phase and in interpretation of system functioning.
    背景与目标: : 起源于人工智能的技术对生物医学的许多领域产生了巨大影响。基于专家的系统已用于开发计算机辅助决策辅助工具。神经网络已广泛用于疾病分类,最近在许多生物信息学应用中,包括基因组学和药物设计。通常,网络理论已被证明可用于建模从医疗组织结构到生化途径的生物医学各个方面。这些方法在设计阶段和系统功能解释中涉及纳米技术的应用中都显示出希望。
  • 【用天然化合物改善阿尔茨海默病治疗的纳米技术。】 复制标题 收藏 收藏
    DOI:10.1007/s13346-019-00694-3 复制DOI
    作者列表:Ramalho MJ,Andrade S,Loureiro JA,do Carmo Pereira M
    BACKGROUND & AIMS: :Alzheimer's disease (AD) is a form of dementia with high impact worldwide, accounting with more than 46 million cases. It is estimated that the number of patients will be four times higher in 2050. The initial symptoms of AD are almost imperceptible and typically involve lapses of memory in recent events. However, the available medicines still focus on controlling the symptoms and do not cure the disease. Regarding the advances in the discovery of new treatments for this devastating disease, natural compounds are gaining increasing relevance in the treatment of AD. Nevertheless, they present some limiting characteristics such as the low bioavailability and the low ability to cross the blood-brain barrier (BBB) that hinder the development of effective therapies. To overcome these issues, the delivery of natural products by targeting nanocarriers has aroused a great interest, improving the therapeutic activity of these molecules. In this article, a review of the research progress on drug delivery systems (DDS) to improve the therapeutic activity of natural compounds with neuroprotective effects for AD is presented. Graphical abstract.
    背景与目标: : 阿尔茨海默氏病 (AD) 是一种痴呆症,在全球范围内具有很高的影响力,占4600万多例。据估计,患者人数将2050年四倍。AD的最初症状几乎是无法察觉的,通常涉及最近事件中的记忆缺失。然而,现有的药物仍然侧重于控制症状,不能治愈疾病。关于发现这种毁灭性疾病的新疗法的进展,天然化合物在AD的治疗中越来越重要。尽管如此,它们仍具有一些限制性特征,例如生物利用度低和穿越血脑屏障 (BBB) 的能力低,这阻碍了有效疗法的发展。为了克服这些问题,通过靶向纳米载体递送天然产物引起了极大的兴趣,提高了这些分子的治疗活性。本文综述了药物递送系统 (DDS) 的研究进展,以提高具有神经保护作用的天然化合物对AD的治疗活性。图形摘要。
  • 【纳米技术作为可注射肠胃外制剂开发的平台: 对知识和最新技术的全面回顾。】 复制标题 收藏 收藏
    DOI:10.3390/pharmaceutics12060510 复制DOI
    作者列表:Shetab Boushehri MA,Dietrich D,Lamprecht A
    BACKGROUND & AIMS: :Within recent decades, the development of nanotechnology has made a significant contribution to the progress of various fields of study, including the domains of medical and pharmaceutical sciences. A substantially transformed arena within the context of the latter is the development and production of various injectable parenteral formulations. Indeed, recent decades have witnessed a rapid growth of the marketed and pipeline nanotechnology-based injectable products, which is a testimony to the remarkability of the aforementioned contribution. Adjunct to the ability of nanomaterials to deliver the incorporated payloads to many different targets of interest, nanotechnology has substantially assisted to the development of many further facets of the art. Such contributions include the enhancement of the drug solubility, development of long-acting locally and systemically injectable formulations, tuning the onset of the drug's release through the endowment of sensitivity to various internal or external stimuli, as well as adjuvancy and immune activation, which is a desirable component for injectable vaccines and immunotherapeutic formulations. The current work seeks to provide a comprehensive review of all the abovementioned contributions, along with the most recent advances made within each domain. Furthermore, recent developments within the domains of passive and active targeting will be briefly debated.
    背景与目标: : 在最近几十年中,纳米技术的发展为包括医学和药学领域在内的各个研究领域的进步做出了重大贡献。在后者的背景下,一个实质性转变的领域是各种可注射肠胃外制剂的开发和生产。实际上,近几十年来,基于纳米技术的可注射产品的市场和管道快速增长,这证明了上述贡献的显着性。除了纳米材料将所结合的有效载荷传递到许多不同的感兴趣目标的能力外,纳米技术已大大有助于本领域许多其他方面的发展。这些贡献包括增强药物溶解度,开发长效局部和全身可注射制剂,通过对各种内部或外部刺激的敏感性以及佐剂和免疫激活来调整药物释放的开始,这是可注射疫苗和免疫治疗制剂的理想成分。当前的工作旨在对上述所有贡献以及每个领域内取得的最新进展进行全面审查。此外,将对被动和主动目标领域的最新发展进行简短辩论。
  • 【纳米技术在角膜新生血管治疗中的应用综述。】 复制标题 收藏 收藏
    DOI:10.1089/jop.2012.0158 复制DOI
    作者列表:Gonzalez L,Loza RJ,Han KY,Sunoqrot S,Cunningham C,Purta P,Drake J,Jain S,Hong S,Chang JH
    BACKGROUND & AIMS: :Nanotechnology is an up-and-coming branch of science that studies and designs materials with at least one dimension sized from 1-100 nm. These nanomaterials have unique functions at the cellular, atomic, and molecular levels. The term "nanotechnology" was first coined in 1974. Since then, it has evolved dramatically and now consists of distinct and independent scientific fields. Nanotechnology is a highly studied topic of interest, as nanoparticles can be applied to various fields ranging from medicine and pharmacology, to chemistry and agriculture, to environmental science and consumer goods. The rapidly evolving field of nanomedicine incorporates nanotechnology with medical applications, seeking to give rise to new diagnostic means, treatments, and tools. Over the past two decades, numerous studies that underscore the successful fusion of nanotechnology with novel medical applications have emerged. This has given rise to promising new therapies for a variety of diseases, especially cancer. It is becoming abundantly clear that nanotechnology has found a place in the medical field by providing new and more efficient ways to deliver treatment. Ophthalmology can also stand to benefit significantly from the advances in nanotechnology research. As it relates to the eye, research in the nanomedicine field has been particularly focused on developing various treatments to prevent and/or reduce corneal neovascularization among other ophthalmologic disorders. This review article aims to provide an overview of corneal neovascularization, currently available treatments, and where nanotechnology comes into play.
    背景与目标: : 纳米技术是一门新兴的科学分支,它研究和设计至少一个尺寸为1-100 nm的材料。这些纳米材料在细胞,原子和分子水平上具有独特的功能。“纳米技术” 一词最早是1974年创造的。从那时起,它发生了巨大的发展,现在由不同且独立的科学领域组成。纳米技术是一个备受关注的主题,因为纳米颗粒可以应用于从医学和药理学,化学和农业,环境科学和消费品等各个领域。快速发展的纳米医学领域将纳米技术与医学应用结合在一起,寻求产生新的诊断手段,治疗方法和工具。在过去的二十年中,出现了许多强调纳米技术与新型医学应用成功融合的研究。这为各种疾病 (尤其是癌症) 带来了有希望的新疗法。越来越清楚的是,纳米技术通过提供新的、更有效的治疗方法,已经在医学领域找到了一席之地。眼科也可以从纳米技术研究的进步中受益匪浅。由于与眼睛有关,纳米医学领域的研究特别集中在开发各种治疗方法以预防和/或减少其他眼科疾病中的角膜新生血管。这篇综述文章旨在概述角膜新生血管,当前可用的治疗方法以及纳米技术的作用。
  • 8 Nanotechnology meets electrophysiology. 复制标题 收藏 收藏

    【纳米技术符合电生理学。】 复制标题 收藏 收藏
    DOI:10.1016/j.copbio.2012.11.014 复制DOI
    作者列表:Kwiat M,Stein D,Patolsky F
    BACKGROUND & AIMS: :Recording of electrical signals from electrogenic cells is an essential aspect to many areas, ranging from fundamental biophysical studies of the function of the brain and heart, through medical monitoring and intervention. Over the past decades, these studies have been primarily carried out by various well-established techniques that have greatly advanced the field, yet pose handicapping technical limitations. Nanotechnology allows the fabrication of devices small enough to enable recording of single cells, and even single neurites. The rise in knowledge in controlling nanostructures allows their tailoring to match cellular components, thus offering high level of interfacing to single cells. We will cover the latest developments in electrophysiology, applying new nanotechnology-based approaches for cellular electrical recordings, both extracellularly and intracellularly.
    背景与目标: : 来自电细胞的电信号的记录是许多领域的重要方面,从对大脑和心脏功能的基础生物物理研究到医学监测和干预。在过去的几十年中,这些研究主要是通过各种成熟的技术进行的,这些技术极大地推动了该领域的发展,但却阻碍了技术限制。纳米技术允许制造足够小的设备,以便能够记录单个细胞,甚至单个神经突。控制纳米结构的知识的增加使它们的剪裁与细胞成分相匹配,从而提供了与单个细胞的高水平接口。我们将介绍电生理学的最新发展,将基于纳米技术的新方法应用于细胞外和细胞内的细胞电记录。
  • 【使用交易区和生命周期分析来了解纳米技术监管。】 复制标题 收藏 收藏
    DOI:10.1111/j.1748-720X.2006.00089.x 复制DOI
    作者列表:Wardak A,Gorman ME
    BACKGROUND & AIMS: :This article reviews the public health and environmental regulations applicable to nanotechnology using a life cycle model from basic research through end-of-life for products. Given nanotechnology's immense promise and public investment, regulations are important, balancing risk with the public good. Trading zones and earth systems engineering management assist in explaining potential solutions to gaps in an otherwise complex, overlapping regulatory system.
    背景与目标: :This article reviews the public health and environmental regulations applicable to nanotechnology using a life cycle model from basic research through end-of-life for products. Given nanotechnology's immense promise and public investment, regulations are important, balancing risk with the public good. Trading zones and earth systems engineering management assist in explaining potential solutions to gaps in an otherwise complex, overlapping regulatory system.
  • 10 An overview of structural DNA nanotechnology. 复制标题 收藏 收藏

    【结构DNA纳米技术概述。】 复制标题 收藏 收藏
    DOI:10.1007/s12033-007-0059-4 复制DOI
    作者列表:Seeman NC
    BACKGROUND & AIMS: :Structural DNA Nanotechnology uses unusual DNA motifs to build target shapes and arrangements. These unusual motifs are generated by reciprocal exchange of DNA backbones, leading to branched systems with many strands and multiple helical domains. The motifs may be combined by sticky ended cohesion, involving hydrogen bonding or covalent interactions. Other forms of cohesion involve edge-sharing or paranemic interactions of double helices. A large number of individual species have been developed by this approach, including polyhedral catenanes, a variety of single-stranded knots, and Borromean rings. In addition to these static species, DNA-based nanomechanical devices have been produced that are ultimately targeted to lead to nanorobotics. Many of the key goals of structural DNA nanotechnology entail the use of periodic arrays. A variety of 2D DNA arrays have been produced with tunable features, such as patterns and cavities. DNA molecules have be used successfully in DNA-based computation as molecular representations of Wang tiles, whose self-assembly can be programmed to perform a calculation. About 4 years ago, on the fiftieth anniversary of the double helix, the area appeared to be at the cusp of a truly exciting explosion of applications; this was a correct assessment, and much progress has been made in the intervening period.
    背景与目标: : 结构DNA纳米技术使用不寻常的DNA基序来构建目标形状和排列。这些不寻常的基序是通过DNA主链的相互交换产生的,从而导致具有许多链和多个螺旋结构域的分支系统。基序可以通过粘性端内聚结合,涉及氢键或共价相互作用。其他形式的内聚涉及双螺旋的边缘共享或副相互作用。通过这种方法已经开发了大量的单个物种,包括多面体的catenanes,各种单链结和Borromean环。除了这些静态物种外,还生产了基于DNA的纳米机械设备,这些设备最终以导致纳米机器人为目标。结构DNA纳米技术的许多关键目标都需要使用周期性阵列。已经产生了各种具有可调特征的2D DNA阵列,例如模式和腔。DNA分子已成功用于基于DNA的计算中,作为Wang tiles的分子表示,可以对其自组装进行编程以执行计算。大约4年前,在双螺旋五十周年之际,该地区似乎正处于真正令人兴奋的应用爆炸的风口浪尖; 这是一个正确的评估,在此期间取得了很大进展。
  • 【纳米技术的抗菌应用: 方法和文献。】 复制标题 收藏 收藏
    DOI:10.2147/IJN.S24805 复制DOI
    作者列表:Seil JT,Webster TJ
    BACKGROUND & AIMS: :The need for novel antibiotics comes from the relatively high incidence of bacterial infection and the growing resistance of bacteria to conventional antibiotics. Consequently, new methods for reducing bacteria activity (and associated infections) are badly needed. Nanotechnology, the use of materials with dimensions on the atomic or molecular scale, has become increasingly utilized for medical applications and is of great interest as an approach to killing or reducing the activity of numerous microorganisms. While some natural antibacterial materials, such as zinc and silver, possess greater antibacterial properties as particle size is reduced into the nanometer regime (due to the increased surface to volume ratio of a given mass of particles), the physical structure of a nanoparticle itself and the way in which it interacts with and penetrates into bacteria appears to also provide unique bactericidal mechanisms. A variety of techniques to evaluate bacteria viability, each with unique advantages and disadvantages, has been established and must be understood in order to determine the effectiveness of nanoparticles (diameter ≤ 100 nm) as antimicrobial agents. In addition to addressing those techniques, a review of select literature and a summary of bacteriostatic and bactericidal mechanisms are covered in this manuscript.
    背景与目标: : 对新型抗生素的需求来自相对较高的细菌感染发生率以及细菌对常规抗生素的耐药性不断增强。因此,迫切需要减少细菌活性 (和相关感染) 的新方法。纳米技术 (使用具有原子或分子尺度尺寸的材料) 已越来越多地用于医学应用,并且作为杀死或减少许多微生物活性的方法引起了极大的兴趣。虽然一些天然抗菌材料,如锌和银,具有更大的抗菌性能,因为颗粒尺寸减小到纳米范围内 (由于给定质量的颗粒的表面体积比增加),纳米颗粒本身的物理结构及其与细菌相互作用和渗透到细菌中的方式似乎也提供了独特的杀菌机制。为了确定纳米颗粒 (直径 ≤ 100 nm) 作为抗微生物剂的有效性,已经建立了多种评价细菌活力的技术,每种技术都具有独特的优点和缺点,并且必须理解这些技术。除了解决这些技术之外,本手稿还涵盖了精选文献的回顾以及抑菌和杀菌机制的摘要。
  • 【使用基于纳米技术的方法跟踪细胞增殖。】 复制标题 收藏 收藏
    DOI:10.2217/nnm-2017-0118 复制DOI
    作者列表:Altea-Manzano P,Unciti-Broceta JD,Cano-Cortes V,Ruiz-Blas MP,Valero-Griñan T,Diaz-Mochon JJ,Sanchez-Martin R
    BACKGROUND & AIMS: AIM:To develop an efficient nanotechnology fluorescence-based method to track cell proliferation to avoid the limitations of current cell-labeling dyes. MATERIAL & METHODS:Synthesis, PEGylation, bifunctionalization and labeling with a fluorophore (Cy5) of 200 nm polystyrene nanoparticles (NPs) were performed. These NPs were characterized and assessed for in vitro long-term monitoring of cell proliferation. RESULTS:The optimization and validation of this method to track long-term cell proliferation assays have been achieved with high reproducibility, without cell cycle disruption. This method has been successfully applied in several adherent and suspension cells including hard-to-transfect cells and isolated human primary lymphocytes. CONCLUSION:A novel approach to track efficiently cellular proliferation by flow cytometry using fluorescence labeled NPs has been successfully developed. [Formula: see text].
    背景与目标:
  • 【电子束合成纳米技术固定透明质酸酶对祖细胞对调控因子敏感性的影响。】 复制标题 收藏 收藏
    DOI:10.1007/s10517-011-1277-0 复制DOI
    作者列表:Dygai AM,Zyuz'kov GN,Zhdanov VV,Udut EV,Miroshnichenko LA,Khrichkova TY,Simanina EV,Stavrova LA,Chaikovskiy AV,Markova TS,Minakova MY,Gol'dberg VE,Artamonov AV,Bekarev AA,Madonov PG,Kinsht DN,Gurto RV
    BACKGROUND & AIMS: :In vitro experiments demonstrated increased colony-forming capacity of erythroid, granulomonocytic, and mesenchymal progenitors of the bone marrow and parenchymal progenitor elements of the liver after treatment with immobilized hyaluronidase. Increased sensitivity of these progenitor cells to erythropoietin, granulocyte colony-stimulating factor, fibroblast growth factor, and stem cell factor, respectively, was demonstrated. Immobilized hyaluronidase enhanced the formation of tissue-specific hepatic CFU against the background of reduced yield of stromal precursors in liver tissue culture containing insulin.
    背景与目标: : 体外实验表明,用固定化透明质酸酶处理后,骨髓的红系,肉芽肿细胞和间充质祖细胞以及肝脏的实质祖细胞元素的集落形成能力增强。证实了这些祖细胞对促红细胞生成素,粒细胞集落刺激因子,成纤维细胞生长因子和干细胞因子的敏感性增加。在含有胰岛素的肝组织培养物中基质前体产量降低的背景下,固定化透明质酸酶增强了组织特异性肝CFU的形成。
  • 【基于纳米技术的治疗慢性皮肤病变的医疗设备: 从研究到临床。】 复制标题 收藏 收藏
    DOI:10.3390/pharmaceutics12090815 复制DOI
    作者列表:Ruggeri M,Bianchi E,Rossi S,Vigani B,Bonferoni MC,Caramella C,Sandri G,Ferrari F
    BACKGROUND & AIMS: :Chronic wounds, such as pressure ulcers, diabetic ulcers, venous ulcers and arterial insufficiency ulcers, are lesions that fail to proceed through the normal healing process within a period of 12 weeks. The treatment of skin chronic wounds still represents a great challenge. Wound medical devices (MDs) range from conventional and advanced dressings, up to skin grafts, but none of these are generally recognized as a gold standard. Based on recent developments, this paper reviews nanotechnology-based medical devices intended as skin substitutes. In particular, nanofibrous scaffolds are promising platforms for wound healing, especially due to their similarity to the extracellular matrix (ECM) and their capability to promote cell adhesion and proliferation, and to restore skin integrity, when grafted into the wound site. Nanotechnology-based scaffolds are emphasized here. The discussion will be focused on the definition of critical quality attributes (chemical and physical characterization, stability, particle size, surface properties, release of nanoparticles from MDs, sterility and apyrogenicity), the preclinical evaluation (biocompatibility testing, alternative in vitro tests for irritation and sensitization, wound healing test and animal wound models), the clinical evaluation and the CE (European Conformity) marking of nanotechnology-based MDs.
    背景与目标: : 慢性伤口,例如压疮,糖尿病性溃疡,静脉性溃疡和动脉功能不全溃疡,是在12周内无法进行正常愈合过程的病变。皮肤慢性伤口的治疗仍然是一个巨大的挑战。伤口医疗设备 (MDs) 的范围从常规和高级敷料到皮肤移植物,但这些都不是公认的金标准。基于最近的发展,本文回顾了基于纳米技术的用于皮肤替代品的医疗设备。特别地,纳米纤维支架是用于伤口愈合的有希望的平台,特别是由于它们与细胞外基质 (ECM) 的相似性以及当移植到伤口部位时促进细胞粘附和增殖以及恢复皮肤完整性的能力。这里强调了基于纳米技术的支架。讨论将集中在关键质量属性的定义 (化学和物理表征,稳定性,粒度,表面特性,纳米颗粒从MDs的释放,无菌性和无菌性),临床前评估 (生物相容性测试,刺激和敏化的替代体外测试,伤口愈合测试和动物伤口模型),基于纳米技术的MDs的临床评估和CE (欧洲一致性) 标记。
  • 【纳米技术联合治疗: 酪氨酸激酶结合金纳米棒和激光热消融在鼠模型中产生肾细胞癌的协同更高治疗反应。】 复制标题 收藏 收藏
    DOI:10.1111/bju.13590 复制DOI
    作者列表:Liu J,Abshire C,Carry C,Sholl AB,Mandava SH,Datta A,Ranjan M,Callaghan C,Peralta DV,Williams KS,Lai WR,Abdel-Mageed AB,Tarr M,Lee BR
    BACKGROUND & AIMS: OBJECTIVE:To investigate tyrosine kinase inhibitors (TKI) and gold nanorods (AuNRs) paired with photothermal ablation in a human metastatic clear cell renal cell carcinoma (RCC) mouse model. Nanoparticles have been successful as a platform for targeted drug delivery in the treatment of urological cancers. Likewise, the use of nanoparticles in photothermal tumour ablation, although early in its development, has provided promising results. Our previous in vitro studies of nanoparticles loaded with both TKI and AuNRs and activated with photothermal ablation have shown significant synergistic cell kill greater than each individual arm alone. This study is a translation of our initial findings to an in vivo model. MATERIALS AND METHODS:Immunologically naïve nude mice (athymic nude-Foxn1nu ) were injected subcutaneously bilaterally in both flanks (n = 36) with 2.5 × 106 cells of a human metastatic renal cell carcinoma cell line (RCC 786-O). Subcutaneous xenograft tumours developed into 1-cm palpable nodules. AuNRs encapsulated in human serum albumin protein (HSA) nanoparticles were synthesised with or without a TKI and injected directly into the tumour nodule. Irradiation was administered with an 808-nm light-emitting diode laser for 6 min. Mice were humanely killed 14 days after irradiation; tumours were excised, formalin fixed, paraffin embedded, and evaluated for size and the percentage of necrosis by a genitourinary pathologist. The untreated contralateral flank tumours were used as controls. RESULTS:In mice that did not receive irradiation, TKI alone yielded 4.2% tumour necrosis on the injected side and administration of HSA-AuNR-TKI alone yielded 11.1% necrosis. In the laser-ablation models, laser ablation alone yielded 62% necrosis and when paired with HSA-AuNR there was 63.4% necrosis. The combination of laser irradiation and HSA-AuNR-TKI had cell kill rate of 100%. CONCLUSIONS:In the absence of laser irradiation, TKI treatment alone or when delivered via nanoparticles produced moderate necrosis. Irradiation with and without gold particles alone also improves tumour necrosis. However, when irradiation is paired with gold particles and drug-loaded nanoparticles, the combined therapy showed the most significant and synergistic complete tumour necrosis of 100% (P < 0.05). This study illustrates the potential of combination nanotechnology as a new approach in the treatment of urological cancers.
    背景与目标:

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