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。

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。

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。

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。

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.

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。

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。

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：

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。

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。

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：

BACKGROUND & AIMS: :The D-trehalose/D-maltose-binding protein (TMBP), a monomeric protein of 48 kDa, is one component of the trehalose and maltose (Mal) uptake system. In the hyperthermophilic archaeon Thermococcus litoralis, this is mediated by a protein-dependent ATP-binding cassette system transporter. The gene coding for a thermostable TMBP from the archaeon T. litoralis has been cloned, and the recombinant protein has been expressed in E. coli. The recombinant TMBP has been purified to homogeneity and characterized. It exhibits the same functional and structural properties as the native one. In fact, it is highly thermostable and binds sugars, such as maltose, trehalose and glucose, with high affinity. In this work, we have immobilized TMBP on a porous silicon wafer. The immobilization of TMBP to the chip was monitored by reflectivity and Fourier Transformed Infrared spectroscopy. Furthermore, we have tested the optical response of the protein-Chip complex to glucose binding. The obtained data suggest the use of this protein for the design of advanced optical non-consuming analyte biosensors for glucose detection.

背景与目标： : D-海藻糖/D-麦芽糖结合蛋白 (TMBP) 是48 kDa的单体蛋白，是海藻糖和麦芽糖 (Mal) 吸收系统的组成部分。在超嗜热古细菌litoralis热球菌中，这是由蛋白质依赖性ATP结合盒系统转运蛋白介导的。已克隆了古细菌T. litoralis中编码热稳定TMBP的基因，并在大肠杆菌中表达了重组蛋白。重组TMBP已被纯化至均一并表征。它具有与本机相同的功能和结构特性。实际上，它具有很高的热稳定性，并以高亲和力结合糖类，例如麦芽糖，海藻糖和葡萄糖。在这项工作中，我们将TMBP固定在多孔硅晶片上。通过反射率和傅立叶变换红外光谱监测TMBP在芯片上的固定。此外，我们已经测试了蛋白质芯片复合物对葡萄糖结合的光学响应。获得的数据表明，该蛋白质可用于设计用于葡萄糖检测的高级光学非消耗分析物生物传感器。

BACKGROUND & AIMS: :The use of a functionalized tip to measure the force of the interaction between ligands and receptors by atomic force microscopy has been discussed for more than a decade, and single-molecule recognition using a functionalized tip from processed samples is achievable now. Techniques for detecting and characterizing specific individual molecules from a living cell are still developing and are discussed in this article. Because many diseases have their roots at the molecular scale and are best understood as a malfunctioning of biologic nanomachines, these techniques should find widespread use in basic biomedical research once the remaining barriers are overcome.

背景与目标： : 使用功能化尖端通过原子力显微镜测量配体与受体之间相互作用的力已经讨论了十多年，并且现在可以使用来自处理过的样品的功能化尖端进行单分子识别。用于检测和表征来自活细胞的特定单个分子的技术仍在开发中，并在本文中进行了讨论。由于许多疾病的根源在于分子规模，并且最好将其理解为生物纳米机器的故障，因此一旦克服了剩余的障碍，这些技术应在基础生物医学研究中得到广泛使用。

BACKGROUND & AIMS: :Deficits or overexpression of neurotrophins cause neurodegenerative diseases and psychiatric disorders. These proteins are required for the maintenance of the function, plasticity and survival of neurons in the central (CNS) and peripheral nervous systems. Significant efforts have been devoted to developing therapeutic delivery systems that enable control of neurotrophin dosage in the brain. Here, we suggest that nanoparticulate carriers favoring targeted delivery in specific brain areas and minimizing biodistribution to the systemic circulation should be developed toward clinical benefits of neuroregeneration. We also provide examples of improved targeted neurotrophin delivery to localized areas in the CNS.

背景与目标： 神经营养蛋白的缺陷或过度表达会导致神经退行性疾病和精神疾病。这些蛋白质是维持中枢 (CNS) 和周围神经系统神经元的功能，可塑性和存活所必需的。已经做出了巨大的努力来开发能够控制大脑中神经营养蛋白剂量的治疗递送系统。在这里，我们建议应开发纳米颗粒载体，以促进特定脑区域的靶向递送并最大程度地减少向体循环的生物分布，以实现神经再生的临床益处。我们还提供了改善向中枢神经系统局部区域靶向神经营养蛋白递送的例子。

BACKGROUND & AIMS: INTRODUCTION:The current COVID-19 pandemic caused by the SARS-CoV-2 virus demands the development of strategies not only to detect or inactivate the virus, but to treat it (therapeutically and prophylactically). COVID-19 is not only a critical threat for the population with risk factors, but also generates a dramatic economic impact in terms of morbidity and the overall interruption of economic activities. AREAS COVERED:Advanced materials are the basis of several technologies that could diminish the impact of COVID-19: biosensors might allow early virus detection, nanosized vaccines are powerful agents that could prevent viral infections, and nanosystems with antiviral activity could bind the virus for inactivation or destruction upon application of an external stimulus. Herein all these methods are discussed under the light of cutting-edge technologies and the previously reported prototypes targeting enveloped viruses similar to SARS-CoV-2. This analysis was derived from an extensive scientific literature search (including pubmed) performed on April 2020. EXPERT OPINION:Perspectives on how biosensors, vaccines, and antiviral nanosystems can be implemented to fight COVID-19 are envisioned; identifying the approaches that can be implemented in the short term and those that deserve long term research to cope with respiratory viruses-related pandemics in the future.

背景与目标：