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| 个人信息 |
| 姓 名： |
张译员 [编号]:3717 |
性 别： |
女 |
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| 擅长专业： |
商贸医药电子机械法律互联网 |
出生年月： |
1988/4/1 |
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| 民 族： |
汉族 |
所在地区： |
天津 天津 |
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| 文化程度： |
硕士 |
所学专业： |
翻译硕士 |
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| 毕业时间： |
0 |
毕业学校： |
南开大学 |
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| 第一外语： |
英语 |
等级水平： |
专八 |
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| 口译等级： |
中级 |
工作经历： |
2 年 |
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| 翻译库信息 |
| 可翻译语种： |
英语 |
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| 目前所在地： |
天津 天津 |
| 可提供服务类型： |
笔译、口译、家教 |
| 每周可提供服务时间： |
周一 周五 周六 周日 |
| 证书信息 |
| 证书名称： |
TEM-8 |
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| 获证时间： |
2012/4/1 |
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| 获得分数： |
良好 |
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| 证书名称： |
TEM-8， Catti2 |
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| 获证时间： |
2012/4/1 |
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| 获得分数： |
良好 |
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| 工作经历 |
| 工作时期： |
2011/9/1--2012/12/1 |
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| 公司名称： |
天津友轮投资管理有限公司 |
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| 公司性质： |
合资企业 |
| 所属行业： |
咨询/顾问 |
| 所在部门： |
翻译部 |
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| 职位： |
翻译 |
| 自我评价： |
工作认真，翻译到位，获得好评 |
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| 工作时期： |
2011/9/1--2012/9/1 |
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| 公司名称： |
天津友轮投资管理有限公司 |
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| 公司性质： |
合资企业 |
| 所属行业： |
咨询/顾问 |
| 所在部门： |
翻译部 |
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| 职位： |
英语翻译 |
| 自我评价： |
工作认真，翻译到位，获得好评 |
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| 笔译案例信息 |
| 案例标题： |
Virtual Issue on Nanomaterials for Drug Delivery |
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| 原文： |
Virtual Issue on Nanomaterials for Drug Delivery
As the development of nanotechnology has extended to the world of biomaterials, a revolution has occurred in the design of nanomaterials systems for drug delivery that have the potential to impact drug e.cacy and patient outcomes signi.cantly for some of our most critical medical challenges, including cancer, infectious disease, and a broad range of genetic disorders. As chemists, materials scientists, engineers, and others begin to apply their expertise and capabilities toward biomedical applications, our ability to manipulate nanotechnology to address these important problems has led to the establish-ment of a burgeoning new .eld that has been heavily represented in ACS Nano since the journal's .rst issue in 2007. From the start, these have been among our most exciting and highest impact papers. In this virtual issue,1 we cover a subset of these articles that address some of the most important aspects of this new world of nanomedicine, as well as many of its challenges and future directions. Some of the most critical themes in the .eld are addressed in the ACS Nano Perspective on the “Impact of Nanotechnology on Drug Delivery”,by Farokzhad and Langer.2 This short article gives insight from the unique perspective of a team that has worked closely at the threshold of translation of nanomaterials from the laboratory to the clinic. At the time of publication of this issue, we are seeing the .rst active, or molecularly targeted, polymeric nanoparticles enter clinical trials, a promising sign for the future of the .eld. The use of nanomaterials has enabled us to address a number of problems with traditional delivery systems, as outlined in the Perspective, including increased bio-availability of the drug, a means of targeting drug delivery to desired cells or tissues, and the potential to combine functionalities within a nanomaterial, such as imaging and delivery.
EDITORIAL
From the start, papers in ACS Nano have addressed nanomaterials for drug delivery. Now, we collect a series of papers in a virtual issue on the topic.
Drug delivery nanoparticles have become key vehicles for the encapsulation and delivery of a range of drugs, including cancer drugs, because their small size enables them to accumulate through the leaky tumor vasculature into the tumor as a means of passive targeting. Both organic and inorganic materials have been examined for nanoparticle deli-very, each with its own set of advantages. Inorganic materials systems often have inherent electrical, optical, or other electromagnetic properties that can be used for multifunction-ality—for example, imaging and delivery—or manipulated to facilitate the delivery and release of drugs in the body. Over the past few years, one of the inorganic materials of great interest has been mesoporous silica, a low-cost, relatively nontoxic, and readily accessible inorganic system that can easily incorporate other inorganic materials for magnetic or
Published online
10.1021/nn2003508
optical properties, while exhibiting surfaces that are easily modi.ed using a range of di.erent surface chemistries. The power and potential of drug delivery using mesoporous silica vehicles was presented by Liong et al.,3 who demonstrated the incorporation of hydrophobic cancer drugs within the
Our ability to manipulate nanotechnology to address these
pores, while creating hydrophilic exterior surfaces with low aggregation and the
important problems has led to the establishment of a
ability to add a range of inorganic com-ponents in these systems. Noble metals,
burgeoning new .eld.
in particular, gold, also present relatively bioinert surfaces that can be readily mod-i.ed for speci.c functions; Ghosh et al.4 demonstrated that modi.cation of gold nanopar-ticles with thiolated-lysine-based functional groups enables the optimization of positive charge on the particles for DNA condensation and delivery; once uptake occurs, however, the gold-thiolate bonds used to modify the particles are reversed in the presence of the naturally occurring glutathione present inside the cell. The group thus takes advantage of the gold-thiol bond to yield the e.ective unwrapping of the DNA in the intracellular environment for high gene transfection and low cytotoxicity. Gold and similar metal nanoparticles can also exhibit unique properties due to the combination of their size and electro-optical properties. Hamad-Schi.erli and co-workers5 used the fact that gold nano-particles of di.erent shape and size absorb light at di.erent wavelengths as a means of selectively melting away gold nanorods with di.erent DNA plasmids bound to their surfaces with ultrafast laser irradiation at the resonance peak of the desired nanoparticle. The ability to deliver a set of di.erent nanoparticle systems intravenously and have them release di.erent cargos at di.erent times by “remote control” is an appealing concept enabled by the unique properties of materials at the nanoscale.
Many newer materials to enter the nanomedicine arena are carbon-based. The use of carbon nanostructures has been extensive in areas such as energy and electronics due to their electrical and optical properties; however, their unique size and structure can also be highly advantageous in drug delivery. Hongjie Dai and co-workers6 illustrated that the graphene sheet composition and high surface area of single-wall carbon nanotubes (SWNTs) enables the use of aromatic π stacking to adsorb large amounts of small-molecule drugs, dye molecule tags, and shield poly(ethylene glycol) (PEG) chains to the surfaces. This noncova-lent attachment can be disrupted at lower biologic pH, and the degree and extent of adsorption is controlled by the diameter of the nanotube, which determines the strengths of these interactions and thus the rate of molecule release in the body. New concepts such as these enable the nanoparticle community to use carbon nanotubes as a new platform for drug delivery. Newer papers have just been published that explore di.erent aspects of carbon nanocarriers. Bhirde et al.7 demonstrate that SWNTs that are covalently conjugated with quantum dots and an anticancer agent, along with a molecular targeting peptide that binds with a receptor overexpressed on tumor cells can lead to targeted tumor cell death, tumor remediation, and simultaneous tumor imaging in animal models. Sengupta and co-workers8 have compared the e.ect on shape of carbon nanocarrier by studying high-aspect-ratio carbon nanotubes and spherical modi.ed fullerene molecules with similar diameter when conjugated with an antitumor drug both in vitro and in vivo. It was found that shape matters a great deal in modulating the angiogenesis of tumors—the growth and maturation of blood vessels—and that this fact can greatly impact the e.cacy of drugs delivered by these two vehicles.
Both self-assembly and various forms of directed assembly have played key roles in developing nanoparticles for delivery; here, a number of organic nanoparticles have often been used to great advantage due to their ability to exhibit a broad range of interactions to generate complexes that can be made permanent or reversible. In the .rst edition of ACS Nano, the cover featured the work of Cortez et al.9 on the development of electrostatic multilayered vesicles that can be designed to contain a broad range of hydrophobic or hydrophilic cargo; the layer-by-layer membrane can serve to protect the cargo on the interior and to regulate its release over time. Cortez et al. demonstrate that the size and the charge of the outer surfaces of these membranes greatly regulate their interaction with cells,
EDITORIAL
and that antibodies or other targeting ligands can be attached to the outer surfaces of these layer-by-layer (LbL) core-shell structures to drive molecular targeting. This past year, Zhang et al.10 demonstrated that two simple modi-.ed polymers—one exhibiting strong positive
This set of papers is a strong sampling of the range of
charge, and the other with strong hydropho-bic interactions—can be designed to interact
chemistries and nanomaterials synthesis techniques used
with each other through a cyclodextrin sugar molecule so as to create complexes that se-
to generate drug delivery nanoparticles.
quester a hydrophobic drug on the interior, and present su.cient positive charge in the exterior water-soluble shell of the resulting complexes as to allow gene complexation. Reversible hydrophobic interactions that can be introduced with increased temperature were used by the Chilkoti group11 to create dynamic ligand-assembling nanoparticles that arrange into more organized structures when heated slightly above body temperature. When the ligand-presenting elastin block copolymers used in this study are heated, the ligand is presented at the surface of the drug complex in high numbers, thus converting the nanoparticle from a low-binding species in the blood-stream to a high avidity targeting nanoparticle once it reaches the tumor, which is heated during treatment, thus avoiding undesired interactions of the nanoparticle while on its way to the targeted tissue.
Along with the use of reversible interactions and molecular assembly, the synthetic capabilities of the chemistry community have had a large impact on the design of new nanomaterials. An example of a more complex chemistry that has enabled the mimicry or ampli.cation of naturally occurring molecules is the highly branched dendrimer. Landmark et al.12 demonstrated the use of the highly functional dendrimer as a means of presenting molecular targeting ligand with high e.cacy and control on the surfaces of iron oxide nanoparticles, demonstrating the use of these highly functional molecules for ligand presentation and particle stabilization. Agrawal et al.13 used positively charged amino dendrimers to functionalize the surfaces of iron oxide nanoparticles in a manner that forms linear functionalized nanoparticle aggregates, or “dendriworms”, that are highly e.ective in the encapsulation and release of siRNA. Hamilton and Harth14 used dendritic molecules with lysine, guanidine, and related functionality to create molecular transporter macromolecules that act much as cell-penetrating peptides in disrupting the cell membrane su.ciently to provide entry of short peptides directly to the cell's cytoplasm.
The ability to mimic the behavior of biological molecules can be particularly enabling when designing routes for cell entry and intracellular release of the drug contents, particularly when it is important to avoid or lessen exposure to the highly acidic environment of the endosome. Bale et al.15 have recently shown the use of silica nanoparticles that have been directly conjugated with protein cargos for rapid cellular uptake via endocytosis; however, these particles rapidly exit the endosome and enable access of the protein in its active form to the cytoplasm. This capability is particularly important for the release of proteins and siRNA, and understanding the mechanisms of release will be one of the future challenges in this .eld. Finally, although most of the work on nanoparticle delivery has relied on the natural sequestration of nanoparticles in the desired tissue and/or on molecular targeting methods to gain accumulation and uptake by the desired cells, another approach to nanoparticle delivery is to let other cells carry the nanoparticle to the targeted tissue. This concept is very new and relies on the ability to modify the surfaces of cells as well as nanoparticles to generate attachments that are stable and do not interfere with the function of the carrier cell. Anderson and co-workers16 demonstrated this concept through the direct attachment of nanoparticles to cell membranes using a pH-sensitive neutravidin-biotin conjugation; stem cells modi.ed in this fashion were able to migrate toward tumors and deliver their cargo within the tumor region.
This set of papers is a strong sampling of the range of chemistries and nanomaterials synthesis techniques used to generate drug delivery nanoparticles. They provide some of the strongest examples of the integration of surface chemistry and its impact on drug delivery e.cacy, as well as demonstrations of the use of organic, inorganic, and hybrid materials systems that are designed to assemble—or disassemble—under desired condi-tions within tumors. Finally, we give examples of basic .ndings regarding the impact of
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| 译文： |
纳米材料在药物给送中的实质问题
随着生物材料领域纳米技术的发展,用于药物给送的纳米材料体系设计发生了一场革命,这不仅可能影响到药物疗效,更会深刻影响到某些疾病的治疗效果,包括,癌症、传染病及各种遗传性疾病,而在这些疾病上人类面临重大的医疗挑战。随着化学家、材料科学家、工程师和其他人不断地将它们的专门知识和能力应用到生物医学领域,我们对纳米技术的应用催生了 一个蓬勃发展的新领域,这一领域在2007年ACS nano创刊以来被大量涉及和讨论。从开始,这些文章就令人振奋，对我们受益颇深。在这个实质问题上,我们选取了其中一部分论述纳米医学新领域最重要的方面及其面临的许多挑战和未来发展方向的文章。在ACS Nano Perspective上发表的Impact of Nanotechnology on Drug Delivery这篇短小精悍的文章中，farokzhad和Langer在实现纳米材料从实验室到诊所转换的最初阶段，从团队合作的独特视角对这一领域最关键的主题进行了论述。这篇文章的出版使我们首次看到了活跃的或靶向分子、聚合纳米微粒进入临床试验研究领域,这是一个一个令人鼓舞的发展迹象。如Perspective中所述，纳米材料的使用已使我们能够用传统的运送体系解决一些问题,包括增加药物生物利用度（将药物定向输送到效应细胞或组织）, 以及探索在纳米材料内结合官能基的可能性,如成像和运输。
从开始,在ACS NANO上的文章就已涉及利用纳米材料进行药物给送。现
在,我们就该实质问题收集了一系列的文章。
用于药物给送的纳米微粒已成为包裹和运送许多药物的主要载体,包
括抗癌药物,因为他们的体积小可以逐渐累积并渗透到有漏隙的肿瘤血管
进而进入肿瘤，这是一种被动靶向方式。纳米微粒药物给送能力已经在有
机材料和无机材料中被检验, 二者各有优势。无机材料系统通常具有内在
电学、光学或其他电磁属性，可用于实现多种功能，例如,成像和输送或促进体
内药物的运输和释放。在过去几年，备受关注的无机材料莫过于介孔二氧
化硅，它是一种低成本的，相对无毒性，可利用的无机体系，它极易与其
它无机材料合并形成其它磁性或电学属性，而同时呈现出使用不同表面化
学成分即可修改的表面，
介孔二氧化硅作为载体药物给送的能量和可能性被Liong et al.提出，他为我们展示了疏水性治癌药物在孔隙内发生的分子合并,这个过程同时产生了亲水性的外表面，其在体系内聚集和增加一系列无机成分的能力低。 贵金属特别是黄金,也相对较而言呈现惰性，表面可以很容易地修改。
Ghosh et al. 论证了基于硫醇盐-赖氨酸基的金纳米微粒官能团能够优化粒子上的正电荷，进而实现DNA缩合和输送;一旦发生摄入,然而，由于细胞中自然存在的谷胱甘肽的影响，用于修改这些颗粒的金硫醇结合物就会被逆转。 因此,小组利用金硫醇结合物在细胞内高细胞转染性和低细胞毒性环境中有效释放DNA。由于纳米微粒的体积和电子光学属性的结合，黄金和类似的金属也可以表现出独特的的属性。Hamad-schifferli和同事利用不同形状和体积的金纳米颗粒会吸收不同波长的光线这一原理，在效应纳米微粒发生共振峰值时，利用超快激光辐射有选择地使用附着在表面的DNA质体溶化金纳米棒。能够在静脉内传输系列纳米微粒体系,并让他们通过"远程控制"在不同时间释放不同的负荷是一个十分吸引人的概念。正是纳米级的材料这种独特的属性使之成为可能。
很多更新材料进入纳米领域是以碳为基础。由于其电气和光学特性，碳纳米构造在很多领域被广泛使用，如：能源和电子领域;然而,其独有的尺寸和结构也使其在药物给送领域占有优势。Hongjie Dai和同事论证了,石墨片层的组成和单壁碳纳米管的高面域能够使共轭芳烃堆积,吸附大量的小分子药物、染料分子附属物并聚乙二醇链到达分子表面。此非共轭键附着物在低生物Ph值环境中可能被破坏，吸附作用的程度和范围的由纳米管的直径控制，以确定这些活动的优势,从而确定分子的释放率。像这种新概念，使得纳米微粒可以借助碳纳米管平台来进行药物给送。探索碳纳米载体的较新一点的论文刚刚出版。像Bhirde et al在论文中展示了与量子点和抗癌物质共轭的单壁碳纳米管，同时，它也与靶细胞肽聚合，当它们进入受主体内，附着在癌细胞上增生便会导致靶向癌细胞死亡，癌细胞修复，同时以动物模型形式实现癌症显像Sengupta和同事已经通过对比研究在与抗癌药物聚合时，体外与体内环境中同直径高纵横比碳纳米管和球形改良富勒烯分子的反应，对比分析了碳纳米载体形状对效用的影响。人们发现，分子形状对于缓和肿瘤血管生成即血管的生长和成熟,具有重要作用。这一事实将对上述两种分子运载药物疗效的发挥产生极大的影响。
自组装和各种形式的定向组装都对形成运载药物的纳米微粒发挥了关键作用;在这里,一些经常使用的有机纳米微粒具有很大的优势,因其能够发挥广泛的作用,影响生成各种复合体,以产生永久的或可逆的影响。 在ACS Nano 第一版，封面便是对Cortez et al研究的专题报道9。他认为，多层囊泡,可进行专门设计,以包含一系列广泛的疏水或亲水负荷;层层细胞膜可以在细胞内保护负荷物,并调节其释放。Cortez et al论证了，外膜表面的体积和电荷将会对负荷物与细胞的相互作用，抗体或其它靶向配体可以附和至层层核壳结构的细胞外表面进行靶向细胞定位。去年，Zhang et al.论证了两种简单的改性聚合物，其中一种呈现很强的正电荷，另一种拥有很强的疏水作用，可以设计通过一个环状糊精糖分子发生作用,以便在细胞内部创建隔离疏水药物的复合物。
在最终产生的复合物中，水溶壳结构外层呈现了充足的正电荷,
以促使基因包合可逆疏水相互作用,可采用提高温度的方法（正是chilkoti小组11所采用的）,来创建所需的动态配体组装纳米微粒,当加热到略高于体温的温度时可以排列成更有组织的结构 当研究中所用的配体结合的弹力蛋白嵌段聚合物被加热时，配体复合物就会在药物表面大量存在,因此当纳米微粒抵达癌细胞就会由血流中的低聚合状态转变为高亲和力的靶向粒子，它在治疗期间也会被加热,从而避免纳米微粒在进入靶向组织时发生不必要的反应。
与可逆作用和分子组装的使用相同,化学分子的合成能力对新纳米材料的设计有很大的影响。 一种促使天然分子增值的更复杂的化学材料是高度支化的树状分子。Landmark et al.12 论证了在氧化铁纳米微粒表面用树状分子来提呈靶向配体具有很高的疗效和使用这些高功能的分子进行配体提呈及粒子稳定。Agrawal et al.13使用了带正电的氨基聚合物使氧化铁纳米微粒功能化以形成功能化线形纳米微粒聚合物或“蛔虫”，它们对于包裹释放短干扰RNA非常有效。Hamilton and Harth14使用了树状分子，赖氨酸胍和相关官能基来创建大分子运载体，作为细胞穿膜肽来破坏细胞膜，使得短肽直接进入细胞质。
当我们设计进入细胞的路线和细胞内药物的释放,特别是当避免或减少暴露在强酸性环境中时，模仿生物分子行为的能力尤为重要。Bale et al.15最近展示了硅纳米微粒直接与蛋白负荷物聚合，通过细胞内容作用产生快速的吸收；然而，这些粒子快速的倒退出来，因而蛋白分子以非常活跃的形式进入了细胞质。在释放蛋白质和短干扰RNA时，这种能力尤为重要，理解这种释放机制将会成为这一领域的挑战之一。最后，尽管关于纳米粒子运载方面大部分文献资料以期望的组织和/或分子定位的自然封存的方法通过效应细胞获得细胞积聚和容入，另一种纳米微粒递送的方法是用其它细胞运载纳米微粒到靶向组织中。这个概念很新，依赖细胞和纳米微粒表面修改，产生稳定并不干扰运载细胞功能的负荷物才能完成。Anderson和同事通过使用Ph敏感形中性抗生物素聚合，将纳米微粒直接负荷到细胞膜。这种形式下的干细胞修复能够缓和癌细胞扩散增生，并在癌细胞区域运载负荷物。
这组论文是对利用化学物质和纳米材料合成技术产生运送药物的纳米粒子这一技术的强有力的采样。文献资料里提供了一些细胞表面化学聚合和其对药物给送有重要作用的的有力例证。也论证了有机材料,无机及混合材料体系在癌细胞中所需环境下被设计聚合或分解。最后，我们就纳米微粒的电荷，体积，形状对于药物给送的影响给予了例证。如今，纳米微粒体系的研究正在如火如荼的进行着，以上只是其中的几个例子，ACS Nano在这一领域为我们提供了令人欢欣鼓舞的重要指导，也展示了在纳米微粒递送及纳米医药方面我们即将面临的挑战。
Paula T. Hammond
副编辑
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